CN102830241B - Various substances holder treating apparatus and method of mentioned treatment - Google Patents

Various substances holder treating apparatus and method of mentioned treatment Download PDF

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Publication number
CN102830241B
CN102830241B CN201210265496.6A CN201210265496A CN102830241B CN 102830241 B CN102830241 B CN 102830241B CN 201210265496 A CN201210265496 A CN 201210265496A CN 102830241 B CN102830241 B CN 102830241B
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carrier
particle shape
particle
nozzle
shape carrier
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CN102830241A (en
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田岛秀二
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Universal Bio Research Co Ltd
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Universal Bio Research Co Ltd
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02Burettes; Pipettes
    • B01L3/0275Interchangeable or disposable dispensing tips
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6804Nucleic acid analysis using immunogens
    • GPHYSICS
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    • G01N30/02Column chromatography
    • G01N30/60Construction of the column
    • G01N30/6047Construction of the column with supporting means; Holders
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • G01N30/02Column chromatography
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    • G01N30/6052Construction of the column body
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
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    • G01N30/6073Construction of the column body in open tubular form
    • GPHYSICS
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    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
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    • G01N33/543Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
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    • B01J2219/00281Individual reactor vessels
    • B01J2219/00286Reactor vessels with top and bottom openings
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    • BPERFORMING OPERATIONS; TRANSPORTING
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    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
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    • B01J2219/00497Features relating to the solid phase supports
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
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    • B01J2219/00497Features relating to the solid phase supports
    • B01J2219/00513Essentially linear supports
    • B01J2219/0052Essentially linear supports in the shape of elongated tubes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277Apparatus
    • B01J2219/0054Means for coding or tagging the apparatus or the reagents
    • B01J2219/00545Colours
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
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    • BPERFORMING OPERATIONS; TRANSPORTING
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    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00596Solid-phase processes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0647Handling flowable solids, e.g. microscopic beads, cells, particles
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0627Sensor or part of a sensor is integrated
    • B01L2300/0636Integrated biosensor, microarrays
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0832Geometry, shape and general structure cylindrical, tube shaped
    • B01L2300/0838Capillaries
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/18Means for temperature control
    • B01L2300/1805Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1827Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • GPHYSICS
    • G01MEASURING; TESTING
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    • G01N2035/00564Handling or washing solid phase elements, e.g. beads
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • GPHYSICS
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    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027General features of the devices
    • G01N2035/1048General features of the devices using the transfer device for another function
    • G01N2035/1055General features of the devices using the transfer device for another function for immobilising reagents, e.g. dried reagents
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
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Abstract

An object of the present invention is to provide a various-substance holder treating apparatus, and a various-substance holder treating method which enable the mutual identification of a plurality of particulate carriers to which various substances are or can be immobilized without the need to arrange the particulate carriers at predetermined positions or in a predetermined order, eliminating the need for time and effort to arrange the various substance at predetermined positions or in a predetermined order to allow treatments to be quickly and easily achieved. The various-substance holder according to the present invention has a plurality of particulate carriers or plural sets of particulate carriers to which plural types of chemical substances are or can be immobilized and a carrier holding portion holding the plurality of particulate carriers or the plural sets of particulate carriers in a substantially stationary state such that the plurality of particulate carriers or the plural sets of particulate carriers can be externally measured. The various-substance holder is configured so that each of the plurality of particulate carriers or at least one of the particulate carriers belonging to the plural sets of the particulate carriers are labeled according to types of the chemical substances or for each of the particulate carriers or each set of the particulate carriers so as to be mutually identifiable before the particulate carriers are introduced and held in the carrier holding portion.

Description

Various matter retaining body treating apparatus and disposal route thereof
The application is application number is 200680032461.0 (international application no is PCT/JP2006/317337), National Phase in China enter day be on March 5th, 2008 (international filing date is on September 1st, 2006), denomination of invention is the divisional application of the Chinese invention patent application of " various matter retaining body, various matter retaining body treating apparatus and disposal route thereof ".
Technical field
The present invention relates to various matter retaining body treating apparatus and disposal route thereof.
Background technology
At present, when have employed the series reaction process of much reagent or material to the target substance becoming check object, such as, described target substance is made to be combined with minichromosome vectors such as microballons and to be housed in vitro.Thereafter, various reagent etc. are injected this test tube, and by being separated by this carrier someway, and transfer in other container by this carrier, reinject other reagent, or carry out the process such as heating.Such as, when this carrier is magnetic, utilizes magnetic field to make it be adsorbed in the inwall of test tube, be separated thus.
In addition, about the process adopting the material being fixed with such as various oligonucleotide the plane carriers such as sample to be carried out to target substance inspection, by carrying out following series reaction process, the base sequence structure of described target substance is studied, described series reaction is treated to: self transferred to by this carrier in the suspending liquid being suspended with and carrying out the target substance identified, or various reagent is injected in this carrier self respectively, maybe this carrier self is transferred in cleaning fluid, or in order to carry out luminous mensuration, this carrier is moved to locating of measuring machine.
In order to carry out these process, the separation of described carrier self and the transfer of carrier self must be carried out, therefore may have process complexity and time-consuming problem of requiring great effort.Especially, with regard to transferring the situation of these carriers self, when being undertaken by manpower, also very large burden may be increased to user, also may cross pollution.In addition, when using robotic movement carrier self, large-scale device is needed.In addition, when carrying out the separation of non-magnetic carrier, need to be separated according to the size of carrier or proportion, there is the complicated and time-consuming problem of requiring great effort of process.
On the other hand, also test tube or plane carrier can not be used, and use be provided with liquid by fluid path pipette tip, be provided with this pipette tip nozzle, to bring the magnetic means in magnetic field to the fluid path of described pipette tip and have and fluid is drawn in this pipette tip and the pipette station of the suction discharge structure making it discharge, and carry out the method for reaction treatment.According to the method, attract the suspending liquid that the many magnetic particles maintaining various material on surface suspend, and make it be subject to the effect in magnetic field when attracting, can effectively this magnetic particle be adsorbed in the described fluid path of pipette tip and be separated etc. thus, but, because magnetic particle can pass through fluid path, therefore, in order to magnetic particle is remained in described pipette tip, need to apply magnetic field and be adsorbed on inwall.For this reason, when processing, need suction to discharge control, combined by the absorption and control in magnetic field, the mobile control of pipette tip.In addition, be the situation of non-magnetic particle about described carrier, the problem (patent documentation 1 ~ 3) be separated is not carried out in existence by this device.
In addition, there is following methods: be held in aperture by the microballon with probe, then, move in kapillary or groove, make microballon according to each kind regulation order arrangement and make probe microballon array, or, make with probe microballon with regulation order influent stream in, and be accommodated in groove or kapillary, thus make the probe arrays (patent documentation 4) of regulation order.
In addition, as for the multiple analysis thing in test fluid sample and the system that shows of real time parsing and carrying out or method, have: there is at least one light source and at least one photodetector, comprise optics in fact at grade, and can communicate with computing machine, possess and can be read by computing machine and to store the storage medium of the order of computing machine, this order comprises the process of certain biological sample using flow analysis device, in this biological sample of the determination in fact simultaneously carried out with treatment step be concerned about at least one analyze the existence of thing and the method (patent documentation 5) of amount.
But, because particle is very little material (such as, several 10 μm ~ number mm) for the process that the mankind carry out, so, when being correctly arranged in groove or kapillary by the order specified in advance by many particles, existence may be wasted time and energy and reluctant problem.In addition, to exist because of the malalignment of particle may not be correctly corresponding problem.In addition, certain flow velocity is being given to the particle of the state floated on a liquid, make it at stream in-pipe, and when carrying out measuring with the photodetector be arranged on outside stream pipe, strictly must follow the trail of particle and measuring one by one, thus exist and apparatus structure may be needed complicated or carry out the problem of complicated control.
Patent documentation 1: Japanese Patent No. 3115501 publication
Patent documentation 2: No. WO96/29602, International Publication
Patent documentation 3: No. WO97/44671, International Publication
Patent documentation 4: Japanese Unexamined Patent Publication 2000-346842 publication
Patent documentation 5: Japanese Kohyo 14-534657 publication
Summary of the invention
So, the first object of the present invention is to provide various matter retaining body, various matter retaining body treating apparatus and disposal route thereof, it makes fixing or can multiple particle shape carriers of the various material such as immobilization of biological substances just can mutually identify not according to the position of prior regulation or order arrangement corresponding to various materials etc., thus, the time and labor arranging various material can be saved, thus fast and the facilitation of process can be realized.
The second object of the present invention is to provide various matter retaining body, various matter retaining body treating apparatus and disposal route thereof, it can not or attract because of absorption and fix by being remained on by this particle shape carrier, also can not because applying the roughly static state of fluid force and action, make the process of each particle shape carrier or measure facilitation and high precision int, using small-scale device to form and just easily can implement process.
The third object of the present invention is to provide various matter retaining body, various matter retaining body treating apparatus and disposal route thereof, and it is applicable to adopt particle shape carrier automatically to carry out the robotization of a series of process such as fixing, transfer, reaction, its mensuration of various material all along.
The fourth object of the present invention is to provide various matter retaining body, various matter retaining body treating apparatus and disposal route thereof, can carry out waiting process to fixing process of particle shape carrier self with the difference place, field of carrying out measuring, and it is easily imported and keeps and measure, thereby, it is possible to improve efficient activity, the reliability of process, the certainty of process of process.
The fifth object of the present invention is to provide various matter retaining body, various matter retaining body treating apparatus and disposal route thereof, easily repeatedly can carry out the secondary immobilization to particle shape carrier arbitrarily, markization, dissociating processes and be held in the mensuration of roughly stationary state, the efficiency of process is high.
The Section 1 of invention is to provide various matter retaining body, it has the set of multiple particle shape carrier or the many group particle shape carriers fixed and maybe can fix number of chemical material, with can hold it in the carrier maintaining part of roughly stationary state from the set of the multiple described particle shape carrier of external measurement or the described particle shape carrier of many groups, each particle shape carrier of described multiple particle shape carrier or belong to each particle shape carrier of at least one of set of each particle shape carrier of many groups, to import and before being held in described carrier maintaining part, according to the kind of described chemical substance, the set of each described particle shape carrier or each described particle shape carrier, by mutual identifiably mark.
At this, " number of chemical material " i.e. various material is the chemical substances such as multiple biological substance, such as, containing boiomacromolecule or low molecular chemical substances such as the inhereditary materials such as nucleic acid, protein, sugar, sugar chain, peptides, this biological substance as part, for as detecting with the combination that this biological substance has a biological substance of the acceptor of associativity, catch, be separated, extraction etc.The inhereditary materials such as described nucleic acid, protein, sugar chain, peptide etc. are had separately to the biological substances such as the inhereditary materials such as the nucleic acid of associativity, protein, sugar chain, peptide and be suitable as acceptor.In addition, as the substitute of biological substance or biological substance, can adopt cell, virus, plasmid etc. biological itself.
So-called " fixing " instigates at least one of described chemical substance directly or the relation being indirectly combined with described particle shape carrier by the material of other kind and being formed.With regard to combination, such as, except utilizing the situation of covalent bond, chemisorption, the situation etc. of physisorption, hydrogen bond, electric interactions is utilized in addition.Or what had by this particle shape carrier is fixed in conjunction with other methods such as the idiosyncrasies between material and various material.In addition, also can form this particle shape carrier with Porous component, concavity and convexity component, cellulosic component, improve thus and the reaction capacity of various material or binding ability.In order to fixing, on described particle shape carrier, such as, occur or generate functional group.For this reason, such as, by to silk be made up of " polyamide-based macromolecule " etc., nylon (3-nylon, 6-nylon, 6,6-nylon, 6,10-nylon, 7-nylon, 12-nylon etc.), PPTA(PPTA) etc. fully aromatic polyamide or be hydrolyzed containing the peptide bond that heteroaromatic polymkeric substance etc. has, to occur or to generate the functional group fixed for biological substance.With regard to the functional group that can be combined with biological substance, such as, there are carboxyl-COOH, amino-NH 2, or its deriveding group.At this, the diameter of the fixing porous of appropriate biological material is such as less than several microns.
So-called " particle shape carrier ", refers to the emboliform solid having and can import and be held in the size of described carrier maintaining part.It is the size of 0.1mm to number mm that the size of this particle shape carrier such as has diameter.Can keep the space segment of this particle shape carrier of maintenance of various matter retaining bodies of this particle shape carrier, its capacity is the space segment except this particle shape carrier kept is such as the volume of number microlitre ~ hundreds of microlitre.Particle shape carrier has solid situation or can accommodate the situation of hollow of material in inside.
As the starting material of " particle shape carrier ",, to liquid sample, there is insoluble material, such as there is the metallic compound such as metal, semiconductor, semimetal, oxidized metal, the dead matter of pottery, glass, silica and so on, the resins such as rubber, latex or polyphenyl styrene, polypropylene, polyester, acrylic acid, the polymer substances such as the fibrous matter such as cellulose, aforesaid nylon, the organic substance of natural materials such as natural fiber such as silk and so on.And then, in detail, about described resin, such as, also comprise the polymkeric substance independent for the monomer shown in below or two or more combination obtained.As the example of monomer, there is the aromatic ethylene compound such as styrene, α-methyl styrene, the esters of acrylic acid such as methyl methacrylate, β-dimethyl-aminoethylmethacrylate or methyl acrylic ester, the vinyl cyanide compounds such as vinyl cyanide, the multifunctional methacrylate compound such as two acrylic acid glycol esters, Ethylene glycol dimethacrylate, the multifunctional aromatic ethylene compound such as divinylbenzene.Meanwhile, acrylic acid, methacrylic acid, styrene sulfonic acid, vinylpyridine etc. can be had the monomer of functional group and aforementioned monomer and use.In addition, as fibrous matter etc., there is the crosslinked of the polysaccharides such as agarose, glucosan, cellulose, carboxymethyl cellulose, the crosslinked of the protein such as the albumin that methylates, gelatin, ossein, casein.Also have, the silk be made up of " polyamide-based macromolecule " etc., nylon (3-nylon, 6-nylon, 6,6-nylon, 6,10-nylon, 7-nylon, 12-nylon etc.), PPTA(PPTA) etc. fully aromatic polyamide or containing the aromatic polymer of heterocycle.In addition, particle shape carrier also can be such as fibrillar, porous plastid, gel body.
So-called " set of particle shape carrier ", refer to the set of the particle shape carrier belonging at least two particle shape carriers, the border of the prior regulation of the position range that the particle shape carrier belonging to this set specifies in advance according to the distance of the prior regulation between the number of regulation in advance, affiliated particle shape carrier, particle shape carrier or the particle shape carrier belonging to surrounding, tunicle or container and specific.Thus, to a particle shape carrier, conclusion process is carried out to the set of particle shape carrier as also resembling.In addition, can resemble have by the particle shape carrier of various substance fixed function, have carry out identificationization function particle shape carrier, other particle shape carrier is (in order to represent the border between set, or in order to mode shield light etc. such as the light not mix markization generation) like that, function is distributed in each particle, make process facilitation, and then other various function can be added.In addition, as long as the situation of the set of particle shape carrier can be identified legibly, just freely can set the number of the particle shape carrier belonged to wherein, therefore, there is extendability, popularity, diversity.
So-called " can measure from outside " refers to, can carry out specific by the state of identifiedization being held in each particle shape carrier of described carrier maintaining part from outside.
So-called " keeping roughly static state " refers to, each particle shape carrier can not freely move in carrier maintaining part, each particle shape carrier, relative to other particle shape carrier, carrier maintaining part or the liquid that has been imported into, is in measurable roughly static state.But, do not need to be completely fixed.
Due to " each particle shape carrier of described multiple particle shape carrier or belong to each particle shape carrier of at least one of set of each particle shape carrier of many groups, to import and before being held in described carrier maintaining part, according to the kind of described chemical substance, the set of each described particle shape carrier or each described particle shape carrier, by mutual identifiably mark ", therefore, do not need, by arrangement by prior regulation, each particle shape vector introduction is held in described carrier maintaining part, information (also comprising order information) according to its position forms the array that just can mutually identify at first.
So-called " particle shape carrier by identifiably mark " means, by discernible identification elements is kept, combines or be fixed on particle shape carrier self, or, identifiably processing or form particle shape carrier self.That is, the reason of markization is present in particle shape carrier, and with the arrangement of such as particle shape carrier or position etc., the situation that the reason of markization is present in outside particle shape carrier is different.Such as, by the shape of particle shape carrier being set as ball, cube, cylinder, quadrangular, circular cone, pyramid, concavo-convex etc. and formed; By carrying out various change to the size of particle shape carrier; By various pigment is paid particle shape carrier; By arrange on particle shape carrier the luminescent substances such as various fluorescent material, phosphorus, chemiluminescent substance, various wavelength the identification elements such as infrared ray, ultraviolet, the electromagnetic radiating matter sending the various wavelength comprising electric wave, the magnetic with various magnetic intensity and carry out mark.Now, the surface that markization is not only included in particle shape carrier arranges the situation of the identification elements such as described luminescent substance, various electromagnetic radiation matter, magnetic, and comprises the situation of the inside being arranged on particle shape carrier.To be arranged on inner situation be particle shape carrier is be formed as hollow and the empty adduction perhaps particle shape container of these materials of harness or the situation of particle shape tunicle wherein.Now, when for luminescent substance, this particle shape container or particle shape tunicle are transparent or semitransparent, when for radiomaterial, must be transparent or semitransparent relative to their electromagnetic wavelength band.Described particle shape carrier has identification elements before importing and be held in described carrier maintaining part, or identifiably processes or form particle shape carrier self.
In addition, described identification elements be can occur with the luminescent substance etc. by measuring discernible prior regulation idiosyncrasy in conjunction with material, also comprise be in the state of also not reacting with this luminescent substance etc. in conjunction with material.As this example in conjunction with material, have relative to the described luminescent substance etc. of ligand binding, described part is had to the acceptor of associativity.This identification elements is potential mark, and by making the reactions such as itself and the prior described luminescent substance specified, markization is come to the surface.Therefore, by using this identification elements, particle shape carrier before importing carrier maintaining part, by potentially, identifiably mark mutually, by the reaction after importing, described mark, by this situation of coming to the surface, is also included within the situation of identifiedization before importing.
Therefore, mutual discernible particle shape carrier positions identifiably arranges, or, need not specify sequentially to make particle shape carrier move, and the set of each particle shape carrier or each particle shape carrier is identified, thereby, it is possible to identify the fixing various materials that maybe can be fixed on this particle shape carrier.Therefore, such as by making described particle shape carrier contact with the suspending liquid that the other method of this various substance reaction or combination identifies the target substance changed, utilize the combination of the mark of target substance and the mark of particle shape carrier, can carry out specific to the various materials being combined with described target substance.
Namely, according to the present invention, even if each particle shape carrier does not form according to having and the position of the corresponding relation of various material or tactic array, and keep random, free, arbitrary or random position or order, also can identify the various materials being fixed with and maybe can fixing this particle shape carrier.
The Section 2 of invention provides various matter retaining body, wherein, described carrier maintaining part has tip (tip) shape container, described cusp-shaped container have can be arranged on carry out gas suction, ejection nozzle on installation peristome and by the suction of described gas, ejection and the inflow of fluid, the oral area of outflow can be carried out.
At this, so-called " cusp-shaped container " has to the installation peristome of nozzle installation and the container for the outflow of fluid, the oral area of inflow.In cusp-shaped container, preferred installation peristome is arranged at upper end, and oral area is arranged at lower end.Cusp-shaped container preferably has and is formed than installation peristome or the thin tubule inserting various container of nozzle, and the front end of tubule is provided with oral area.Also preferably be provided with the storing section of the stored liquid being communicated with installation peristome and tubule.This is because described tubule is formed thinner than described installation peristome, therefore can not directly be communicated with.As this storing section, preferably there is the extra heavy pipe thicker than described tubule.Tubule has the situation that to be set to one with described storing section or extra heavy pipe and is set to removably situation.When being set to freely to load and unload, described carrier is easy to the collecting in tubule.This extra heavy pipe and tubule are not limited to have this large diameter part and typical, the situation with the shape of point head of small diameter part being equivalent to be communicated with tubule.Such as, also with there is the pipe belt of four prism type shape for large diameter part, also thin diameter tube can be replaced by the pipe belt of prism tubular.In addition, the internal diameter of described tubule or the size in cross section less than the internal diameter of the nozzle being installed on described installation peristome.In addition, described carrier is housed in tubule.The volume of this tubule preferably has the scope of several microlitre ~ hundreds of microlitre.
In order to carry out optical detecting, the preferred at least thin tube part of material of cusp-shaped container is divided into the material of light transmission.As the material of cusp-shaped container, such as, there are the resin of tygon, polypropylene, polystyrene, acrylic acid etc., glass, metal, metallic compound etc.Size such as accommodating the size of number microlitre ~ hundreds of microliters of liquid in tubule.
In addition, particle shape carrier as described later, has the situation in the tubule being housed in described cusp-shaped container, is housed in the situation of described storing section or is housed in the situation in both this.When being housed in storing section, the core that insertion maybe can insert storing section is provided with in storing section, groove or the ridge of such as spiral fashion, zigzag, linearity, the shape that crawls is provided with at the outside surface of described core, thus, between the inwall and groove of storing section or between the inwall of storing section and the outside surface of core and ridge, form thin path, sometimes along this path collecting particle shape carrier.Or, there are groove or ridge that above-mentioned shape is set at the inwall of storing section, thus between water jacket and the outside surface of described core or form the situation of thin path between the outside surface of the inwall of described storing section and ridge and core; On both the inwall of storing section and core, groove or the ridge of above-mentioned shape are set, thus form the situation of thin path.These paths are formed as described particle shape carrier can be arranged in the such size of row.In these cases, make tubule self form spiral fashion etc. with described later and keep compared with the situation of particle shape carrier, compact and there is rigidity.In addition, path described in these is arranged in the mode be communicated with described tubule, keeps the mode of particle shape carrier also passable continuously in described storing section and tubule.
The Section 3 of invention provides various matter retaining body, wherein, described cusp-shaped container has the storing section that can store liquid and have described installation peristome and is communicated with described storing section and has the tubule that described in the ratio of described oral area, storing section is thin, and described particle shape carrier is maintained in described tubule.
Now, as long as described particle shape carrier is remained in described tubule with row, just by scanning along described tubule described particle shape carrier, thus more easily can measure.At this, because be row, so the diameter of described tubule or the cross section vertical with axis need to have described particle shape carrier and can not interlock vertically or can not arrange plural shape or size with on axially vertical direction.That is, tubule is designed to, there is larger than the external diameter of this particle shape carrier, less than the twice of this external diameter internal diameter or width and length.
So, can scan along described row each particle shape carrier and measure.The external diameter of this particle shape carrier is such as about 0.1mm ~ about 3mm, and described tubule such as has the internal diameter of about 0.2mm ~ about 6mm.
Tubule is not limited to linearity, for curve-like is also passable.Such as, the spiral fashion that the cylinder linking the surrounding of the axle of oral area and installation peristome for edge rotates or planar spirally rotates; Or have sweep or have U-shaped part can.With regard to tubule, not only there is the situation of circle or ring-type in the cross section perpendicular to fluid flow direction, and the cross section of inwall also can be such as square.When the particle shape carrier that should keep is spherical, square vertex as fluid by the effect of groove.
The Section 4 of invention provides various matter retaining body, wherein, in described carrier maintaining part, have with can with the state of the fluid contact flowed into from described oral area, the inclosure portion described particle shape carrier enclosed in described carrier maintaining part.
At this, example as " inclosure portion " is, have and described installation peristome or the mode that separates relative to this maintaining part between peristome and described oral area be arranged on one or more carrier on other component by stoping component, to make fluid pass through described carrier not by.
" carrier is by stoping component " is the component formed by the component different from described cusp-shaped container.Also can to combine use by this cusp-shaped wall of a container etc. with to the wall of a container that this cusp-shaped wall of a container is processed.Described carrier is by stoping component, and owing to forming gap between itself and the internal face of container, so fluid can pass through, but the size in its through hole or gap is the intransitable size of particle shape carrier or shape.Be such as the component that the mode separated by tubule with wheel shape, cruciform, in-line, radial, netted or ring-type is arranged, there is the connectivity porous member of through hole.When for connectivity porous member, for the various particle shape carriers with the size larger than aperture, can positively enclose.Described " connectivity porous member " does not need for any filtrator of catching material by adsorbing.But, when this inclosure portion is the film-form such as filtrator, diaphragm filtrator, the outflow of the described carrier from oral area or installation peristome can not only be prevented, and the material of regulation can be caught.In addition, when being arranged on the component different from cusp-shaped container in inclosure portion, use the component being formed as the thin lamellar or film-form of the flow direction of fluid, or be used in the large connectivity porous member in aperture under condition that carrier can not flow out.In order to prevent described particle shape carrier from the outflow of described oral area and the outflow from described installation peristome simultaneously, described carrier, by stoping the number of component, is preferably arranged at least two in the mode being clipped this particle shape carrier by oral area side and installation peristome side.
In addition, by being set to freely to load and unload by stoping component by the described carrier be arranged on other component, inclosure and the extraction of described carrier can easily be carried out.
In addition, as inclosure portion, when arranging when processing cusp-shaped container, under the condition that carrier can not flow out, opening portion being designed to larger size, the pressure sucked required for ejection can be reduced thus.As the situation employing cusp-shaped container self, have to make described tubule attenuate in the mode reduced and be provided with the situation to the outstanding lug boss of the center direction of pipe, or there is the situation making the wall of described maintaining part towards one or more the teat given prominence in the isolated direction of described installation peristome and described oral area.
Thus, particle shape carrier is not processed, and make it be out of shape by processing described cusp-shaped container, particle shape carrier positively can be enclosed.
The Section 5 of invention provides various matter retaining body, and wherein, entirety or the part of the wall of described carrier maintaining part are formed by the electroconductive member with regulation resistance value.
At this, by electroconductive member being arranged in described cusp-shaped container, the terminal connected being contacted with this electroconductive member, electric current can be made to flow through and there is this electroconductive member of regulation resistance value and make it generate heat with the power circuit being arranged at outside.For this current value, controlled according to contents processing by control part described later.
In addition, as " regulation resistance value ", be can carry out necessary heating by making the electric current of regulation flow in described electroconductive member, with the value making this electroconductive member reach the temperature corresponding with object.Such as, so-called sheet resistance value, per unit area is such as about hundreds of Ω ~ approximate number Ω, and in addition, the resistance value can carrying out induction heating is such as number more than Ω cm.
As " electroconductive member ", such as, it also can be the metallic compound such as metal, metal oxide; The conductive materials such as alloy, semiconductor, semimetal, electroconductive resin; By the material that these conductive materials and non-conducting material such as pottery, glass, synthetic resin etc. are combined; Or, by conductive material combination with one another material together.Sometimes, the component such as will formed by aluminium, aluminium oxide, tin oxide, iron, ferroalloy, nickel-chrome, two or more different conductive materials, by bonding, welding, engages and combines.By making electric current flow in these components, or when for iron, ferroalloy, by applying the magnetic field changed in time, induction heating can be carried out to these components.When two kinds of conductive materials are bonded together, Bel's base of a fruit dust (ベ Le テ ィ エ) effect can be utilized, carry out heating and cooling according to sense of current.
The shape of electroconductive member has wire, film-form, foil-like, membranaceous, lamellar, tabular, elongated shape, stratiform etc.In order to strengthen electroconductive member, the component that also bonding for this electroconductive member, welding, evaporation can be formed in non-conductive components.This electroconductive member is controlled in set point of temperature according to " electromagnetic signal " (electric signal or magnetic signal).In this electromagnetic signal, due to apply heat or cold air thermodynamics signal except.
In addition, described wall, inner wall surface thereof is towards in described cusp-shaped container, and its outside wall surface is positioned at outside this cusp-shaped container, is the cusp-shaped container be integrally formed between internal and external walls face.That is, the wall portion clamped by internal face and the outside wall surface of cusp-shaped container, the solid state being such as metal, resin etc. or bonding them together, and form wall in the mode that can not freely be separated.Therefore, the part of or wall overall as wall and the electroconductive member that formed, when there is the electroconductive member from wall is freely separated, such as, the electroconductive member only only contacted with wall or be detachably arranged on electroconductive member on wall with screw etc., by the electroconductive member can detachably installed relative to other component be arranged on wall, and the electroconductive member that departs from completely of wall such as weld, owing to splitting, therefore.For this reason, as long as cusp-shaped wall of a container sets electroconductive member in the mode reaching the thickness required by cusp-shaped wall of a container, just can suppress the size of cusp-shaped container or the scale of device entirety, thus process with paying no attention to the existence of heating arrangement.
The Section 6 of invention provides various matter retaining body, wherein, the set of each group of described particle shape carrier at least has two independent particle shape carriers arranged, wherein at least one particle shape carrier is the fixing reaction particle maybe can fixing each chemical substance, and at least one particle shape carrier is in addition can by the mark particle of the set of the kind of described each chemical substance or described particle shape carrier identifiably mark.
At this, as " reaction particle ", as illustrated in particle shape carrier, desirably have and fully fixedly can have the material of surface-active material or chemical substance (reactive material) or the particle of character.On the other hand, as " mark particle ", desirably by material that fluorescent material, chemiluminescent substance, radiomaterial are coated; By the material that various pigment is coated; Or, there is the particle of discernible regulation shape such as cube, cylinder, square column, circular cone, cross shape etc.; There is the particle of discernible prescribed level; Or, adopt the material carrying out in these fluorescent materials, chemiluminescent substance, radiomaterial or part or all in regulation shape combining.In addition, as these mark particles, as long as have the particle of the character of the material that can adhere to described various material or there is with it associativity.
The Section 7 of invention provides various matter retaining body, wherein, the set of each group of described particle shape carrier at least has two independent particle shape carriers arranged, and wherein at least one particle shape carrier is the set impact each other getting rid of the particle shape carrier that markization is brought or the border particle determining mutual border.
At this, markization comprises the situation of described reaction particle being carried out self to markization, after being also included within reaction, based on the second mark described later, and the situation of reaction particle identifiedization.When reaction particle and other particle have been carried out markization, also can belong to the situation of a set at least three particle shape carriers of reaction particle, markization particle and border particle, and markization particle is as border particle and at least two particles belong to a situation about gathering.In addition, as the example of " border particle ", such as, the particle formed by the metal with the light-proofness covering the light such as fluorescence, chemiluminescence, pottery etc. is had.
Eight of invention provide various matter retaining body, wherein, in the outside surface or described carrier maintaining part of described particle shape carrier, maintaining any one party of inwall of particle shape carrier part, be provided with one or more protuberance separately, or, be provided with one or more ridge or groove.
At this, so-called " in carrier maintaining part, maintaining the part of particle shape carrier " is such as the tubule part keeping particle shape carrier with row.Thus, have cylindrical inner or described inclosure portion has circular through hole even if particle shape carrier is spherical, tubule, described particle shape carrier also can not touch with the inwall of carrier maintaining part or block the flowing of through hole and block fluid.
The Section 9 of invention provides various matter retaining body, and wherein, maintain in the described carrier maintaining part of described particle shape carrier, the volume can accommodating the space of fluid is approximate number microlitre ~ approximate number hectolambda.
At this, so-called " can accommodate the space of fluid ", generally refers to the space formed between the surface of the carrier having enclosed this tubule and the internal face of tubule.
By limiting like this volume of tubule, even if the liquid namely liquid of small quantity being counted microlitre ~ hundreds of microlitre volume sucks tubule, also can make this liquid as the surface of described carrier or contacting equably.This small quantity typically refers in biological chemistry, especially in DNA field, easily can extract the amount of substance of row relax of going forward side by side in biology.In addition, described cusp-shaped container, except tubule, is provided with the extra heavy pipe be communicated with this tubule, such as, by having the volume of several times ~ tens of quilt of tubule volume, can process various liquid measure.
The Section 10 of invention provides various matter retaining body treating apparatus, and it has: have carry out gas suction, ejection the shower nozzle of one or more connected nozzle, the suction of gas, the suction emitting mechanism of ejection is carried out via described nozzle, with the set with multiple particle shape carrier or the many group particle shape carriers fixed and maybe can fix number of chemical material, and install and maybe can be arranged on described nozzle and the carrier maintaining part of roughly stationary state can be held it in from the set of particle shape carrier multiple described in external measurement or described many group particle shape carriers, each particle shape carrier of described multiple particle shape carrier or belong to each particle shape carrier of at least one of set of many group particle shape carriers, to import and before being held in described carrier maintaining part, according to the kind of described chemical substance, the set of each particle shape carrier or each particle shape carrier, by one or more various matter retaining bodies of mutual identifiably mark.
At this, " various matter retaining body " is the various matter retaining bodies of invention any one of the invention of the first to Section 9.Especially, this various matter retaining body must be installed and maybe can be arranged on described nozzle.
The Section 11 of invention provides various matter retaining body treating apparatus, and it has: collecting maybe can accommodate the liquid storage portion group of various liquid; Make the mobile device of described shower nozzle and described liquid storage portion faciation movement over the ground; With based on by described various matter retaining body structure, be fixed on described particle shape carrier or be present in the kind of the various materials in fluid, material conditions that concentration, amount of liquid, the coordinate position that comprises the collecting position of described liquid are formed and contents processing, the control part that the amount sprayed the suction of described nozzle, speed, number of times, time or position control.
At this, " contents processing " is such as correspond to processing intent, according to the rules order or stipulated time program list repeat containing and composite reaction, cleaning, transfer, dispensing, separation, extraction, heating, cooling, clarification, mensuration, mix, deviate from, stripping, stirring etc., or their a series of process." time " comprises the duration or timing that suck ejection.By setting duration or timing, the setting of intermittent, continuous print or interrupted suction, ejection can be carried out.
When carrying out " reaction " and processing, such as, according to described material conditions, containing the container position of this reagent, with regulation speed and with the carrier of described tubule enclose region volume such as 80% liquid measure, to by described conditional decision described suction, ejection repeatedly control.It is sucked to the number of times of ejection, also carry out the control specified according to described material conditions.Such as, when carrying out " cleaning " and processing, according to described material conditions, contain the container position of cleaning fluid, with the speed of the regulation determined according to this process, to described suction, spray the control repeatedly carrying out stipulated number.Similarly, the control sprayed corresponding to the suction of described process can be carried out.As " speed ", such as, when the material processed is DNA, because its size is less than protein, so, in order to improve DNA meeting property each other, must speed be improved.In addition, speed is different because of the content difference of process, and the situation of cleaning or stirring is compared with carrying out the situation of reaction treatment, and it sucks, the speed of ejection diminishes.
The shape that " structure of various matter retaining body " also comprises this tip, enclose particle shape carrier position, by the shape or character etc. of particle shape carrier of accommodating or the shape etc. in inclosure portion.So-called to suck according to " kind of chemical substance " regulation, the action of ejection, such as, as the inhereditary materials such as DNA, when usually little than the size of protein, a little and fireballing side is easy to process process liquid measure.This is because size is less, meeting property is lower usually.
At this, described various matter retaining body, such as, have and be arranged on the installation peristome on this nozzle and the suction by described gas, ejection and the inflow of fluid can be carried out, the oral area flowed out, and there is the cusp-shaped container of the tubule thinner than described nozzle, the biological substance of regulation can be fixed and maybe can be fixed on from the multiple different particle shape carriers of the discernible prior regulation in outside and the size had by described oral area or shape, and have with the state that can contact with the fluid flowed in described holder, this carrier is enclosed the inclosure portion be arranged on described cusp-shaped container in this holder.
The Section 12 of invention provides various matter retaining body treating apparatus, it has: the receiving trap receiving the signal from the described particle shape carrier being held in described carrier maintaining part, and carries out the resolver of resolving based on the signal from described receiving trap.
At this, " reception of signal " comprises coming the reception of the electromagnetic wave signal of the various frequency bands of the light of self-contained light signal.The reception of receiving trap has: to be installed on there is described multiple connected nozzle shower nozzle on multiple particle shape carrier holders situation of carrying out in the lump and the situation of successively each described various matter retaining body being carried out to light by receiving trap.When for the latter, be used in the mobile device of relative movement between described receiving trap and described container, described tip or receiving trap are one by one carried successively relatively, while carry out light.Now, because measure staggering time to carry out, so, when carrying out the extraction of a part of reagent such as DNA, the PCR reactant liquor used in the pre-treatment of PCR, or in the situation such as the injection of matrix liquid in chemiluminescent situation, all must carry out dispensing before being about to reaction or before the certain hour of reaction.Therefore, dispensing can not be carried out simultaneously, and the ground setting-up time difference and carry out dispensing of preferably staggering one by one temporally.In addition, when measuring fluorescence, irradiation regulation being also set in described container and exciting the light-emitting device used up.
The Section 13 of invention provides various matter retaining body treating apparatus, wherein, described resolver is according to the signal based on the first mark received by described receiving trap and resolve based on the signal of the second mark, described first mark is at described vector introduction and before being held in described carrier maintaining part, the mark that mutually can identify according to the set of the kind of described chemical substance, each described particle shape carrier or each particle shape carrier; Described second mark is at described vector introduction and after being held in described carrier maintaining part, by the mark of described particle shape signal of carrier.
At this, " signal based on the first mark " must be that to belong to the particle shape carrier of the first mark identified, and mutually can identify each other at the signal based on the first mark.Further, " signal based on the second mark " must be that to belong to the particle shape carrier of the second mark identified, and mutually can identify each other at the signal based on the second mark.Therefore, between " signal based on the first mark " and " signal based on the second mark ", must mutually can identify.In addition, according to the intensity of signal identified based on second or the quantities received of signal, the reacting dose of carrier and described various material can be measured.
The Section 14 of invention provides various matter retaining body treating apparatus, wherein, in the outside of described carrier maintaining part, near to or in contact with, can close to or gradient of temperature body can be provided with contiguously, described gradient of temperature body according to the signal from outside make temperature rise, decline.
At this, " gradient of temperature body " refers to component or the device that can make the rising of its temperature or decline according to the signal from outside.When described gradient of temperature body is electroconductive member, " signal " is electromagnetic signal, i.e. the signal of electric or magnetic generation.Also can utilize gradient of temperature health check-up testing temperature, and produce signal based on this temperature.
In addition, be preferably designed for can relative movement to described various matter retaining body for described gradient of temperature body.In addition, in this case, described control part, except the control carried out sucking, spray, also carries out the control of temperature based on the content of process.
The Section 15 of invention provides various matter retaining body treating apparatus, and wherein, described shower nozzle is that multiple connected nozzle block and an independent nozzle form along column direction arrangement, described suction emitting mechanism carries out suction, the ejection of gas to the nozzle block of described shower nozzle and independent nozzle simultaneously, described mobile device has shower nozzle mobile device and ranks delivery pathways device, described shower nozzle mobile device makes described shower nozzle relatively move in the row direction for the platform with described liquid storage portion group, described ranks delivery pathways device have comprise described nozzle block mobile route on along the row transport path of described column direction, and along the transport path of the row transport path of described line direction on the mobile route of described single nozzles, and the conveying resettlement section can accommodated respectively from the liquid of the shower nozzle ejection connected together described in the cusp-shaped container that can load and unload in described nozzle block or oneself is carried along described transport path.
At this, " column direction " and " line direction " is not necessarily orthogonal with Y-direction (longitudinal direction) as X-direction (transverse direction), and oblique is also passable." shower nozzle connected together " and " independent shower nozzle " also can move independently.In addition, described ranks delivery pathways device has row transport path on the mobile route being positioned at described shower nozzle and row transport path, such as, also can have square shape or the closed transport path such as polygon-shaped, also can have open transport path.
At this, " conveying resettlement section " is the part of accommodating tip or liquid in described conveying device, and preferably at least having with the nozzle number of the shower nozzle connected together is the conveying resettlement section of equal number.
The Section 16 of invention provides various matter retaining body treating apparatus, wherein, in the assigned position of the described transport path along described ranks delivery pathways device, be provided with the receiving trap received from the removably signal of described cusp-shaped container or described conveying resettlement section.
The Section 17 of invention provides various matter retaining body manufacturing installation, it has carrier capture portion and carrier catches moving part, described carrier capture portion can catch the particle shape carrier of the multiple particle shape carrier fixed and maybe can fix number of chemical material or the set belonging to many group particle shape carriers, each particle shape carrier of described multiple particle shape carrier or belong to each particle shape carrier of at least one of set of many group particle shape carriers, according to the kind of described chemical substance, mutual identifiedization of set of each described particle shape carrier or each particle shape carrier, described carrier is caught the particle shape carrier that moving part makes described carrier capture portion catch and is moved together with carrier capture portion, and described carrier capture portion makes caught particle shape carrier move to can keep multiple described particle shape carrier or the set organizing particle shape carrier more, can carry out from outside measuring and make it remain on the carrier maintaining part of roughly stationary state, thus manufacture various matter retaining body.
At this, " carrier catches moving part " such as has: the sucting of breathable gas; The suction being communicated with, utilizing this sucting with this sucting can catch the tubular element of described particle shape carrier; Make described tubular element itself and Section 1 invent invent to Section 9 in relatively-movable tubular element mobile device between arbitrary carrier maintaining part.Tubular element such as one by one catches described particle shape carrier with its front end.
The Section 18 of invention provides various matter retaining body manufacturing installation, wherein, described carrier maintaining part is cusp-shaped container, there is the suction that can be installed on and carry out gas, installation peristome on the nozzle of ejection, with the suction by described gas, spray and can flow out, the oral area of incoming fluid, also there is the cusp-shaped vessel leg making described installation peristome or oral area support described cusp-shaped container upward, around by around the described installation peristome upward of described cusp-shaped container that supports or oral area, the funnel-form guide expanded upward, with towards the described oral area downward of described cusp-shaped container or the below suction structure of installation peristome suction gas.
The Section 19 of invention provides various matter retaining body manufacturing installation, and it has collecting and maybe can accommodate the carrier resettlement section group of various particle shape carrier and accommodate the carrier maintaining part resettlement section of described carrier maintaining part.
The Section 20 of invention provides various matter retaining body manufacture method, it comprises: constant mark chemical industry sequence, number of chemical material is fixed on multiple described particle shape carrier, according to the kind of its chemical substance, each particle shape carrier or each set comprising the particle shape carrier of particle shape carrier, to the particle shape carrier being fixed with described chemical substance, multiple particle shape carriers of chemical substance can be fixed, or the particle shape carrier being fixed with chemical substance maybe can fix chemical substance particle shape carrier beyond particle shape carrier, by mutual identifiably mark, import and keep operation, by the set of described multiple particle shape carrier or many group particle shape carriers can to measure from outside and roughly stationary state imports and is held in carrier maintaining part.
The Section 2 of invention provides various matter retaining body manufacture method, wherein, described importing keeps operation to have: import operation, by be fixed with described chemical substance, maybe can fix chemical substance, by mutually identifiably multiple particle shape carrier of mark or the set of many group particle shape carriers be transplanted on described carrier maintaining part, then import in described carrier maintaining part; Keep operation, the set of the multiple particle shape carrier or many group particle shape carriers that import described carrier maintaining part is enclosed described carrier maintaining part and kept roughly stationary state.
At this, described importing keeps operation such as to carry out as follows: utilize the tubular element being communicated with, can keeping in its front end particle shape carrier with the sucting of suction gas, described particle shape carrier is held in its front end, then the particle shape carrier resettlement section of this tubular element from the platform containing particle shape carrier is transplanted on described carrier maintaining part.
The Section 22 of invention provides various matter retaining body disposal route, it has: installation procedure, multiple particle shape carrier of number of chemical material or the set of many group particle shape carriers maybe can be fixed by fixing, can to measure in outside and roughly static state is held in one or more carrier maintaining part, described carrier maintaining part has the suction that can be arranged on and carry out gas, installation peristome on the one or more connected nozzle of ejection and the suction by gas, ejection and the inflow of fluid can be carried out, the oral area flowed out, and by each particle shape carrier of described multiple particle shape carrier or each particle shape carrier of at least one belonging to the set organizing particle shape carrier more, according to the kind of described chemical substance, the set of each described particle shape carrier or each described particle shape carrier, import and before being held in described carrier maintaining part by mutually identifiably one or more various matter retaining bodies of mark be installed on described nozzle, reaction process, makes described nozzle relative movement, and makes the oral area of described various matter retaining body move to the liquid storage portion of one or more regulation successively, thus makes the liquid comes into contact in described particle shape carrier and liquid storage portion and react, resolve operation, resolve based on the received signal from each particle shape carrier be held in described carrier maintaining part.
At this, have can be arranged on installation peristome on nozzle and by the suction of gas, ejection and the inflow of fluid can be carried out, the carrier maintaining part of the oral area of outflow is cusp-shaped container.
The Section 23 of invention provides various matter retaining body disposal route, wherein, described parsing operation according to receive in described reception operation, based on first mark signal and based on second mark signal resolve, described first mark is at described vector introduction and before being held in described carrier maintaining part, according to the mutual discernible mark of set of the kind of described chemical substance, each described particle shape carrier or each particle shape carrier; Described second mark is at described vector introduction and after being held in described carrier maintaining part, described particle shape carrier is carried out to the mark of markization.
In addition, if the first mark such as carries out mark with fluorescent material, the second mark utilizes chemiluminescent substance to carry out mark, then in order to receive the signal based on the first mark, undertaken by irradiating exciting light to this particle shape carrier.In addition, after reaction process, in order to be undertaken based on the signal of the first mark and the reception of signal based on the second mark by single pass, such as can according to the mark of each particle shape carrier, by repeatedly opening or closing excitation light pulse to receive.
The Section 24 of invention provides various matter retaining body disposal route, wherein, described reaction process is: the nozzle being provided with described various matter retaining body is moved to the liquid storage portion of specifying, based on the structure by described carrier maintaining part, be fixed on described particle shape carrier or be present in the kind of the chemical substance in liquid, concentration, amount of liquid, the material conditions that the position coordinates comprising the collecting position of described liquid is formed and contents processing, to comprising the amount sprayed via the suction of described nozzle, speed, number of times, the action of the suction ejection of time and position controls, thus, the chemical substance making to be fixed in described particle shape carrier be housed in the liquid comes into contact in described liquid storage portion and react.
The Section 25 of invention provides various matter retaining body disposal route, and it has after described reaction process, receives the reception operation of the signal from the described particle shape carrier be maintained in described carrier maintaining part.
In addition, with regard to the described signal based on the first mark, because it is irrelevant with reaction, so, received also passable before described reaction process.With regard to described based on second mark signal with regard to, receive after described reaction process.Therefore, in this case, the scanning along described particle shape carrier at least will be carried out twice.On the other hand, after reaction process, to the signal based on the first mark and when receiving based on the signal of the second mark, just can complete with single pass.
The Section 26 of invention provides various matter retaining body disposal route, and wherein, described reaction process has the gradient of temperature operation making the temperature in described carrier maintaining part rise, decline.
Invention effect
According to Section 1 or the Section 20 of invention, the set of particle shape carrier or particle shape carrier, to import and before remaining on carrier maintaining part, according to the set of the kind of described various material (number of chemical material), each described particle shape carrier or each particle shape carrier, carry out mutual discernible markization.Therefore, when importing to carrier maintaining part and keep, do not need to mutually identify that various material is formed by each particle shape bearer configuration in the array of the position of the prior regulation corresponding with various material, each particle shape carrier does not have the random of corresponding relation or arbitrary position with various material or is keeping roughly stationary state with random or arbitrary order.Therefore, the time and labor arranging various material can be saved, thus can easily and promptly carry out importing and keeping.
In addition, according to the present invention, because do not need based on corresponding with this particle shape carrier and additional position, to the array that the various materials being held in described particle shape carrier identify, so, do not need each particle shape carrier to be strictly fixed on each position or strictly to maintain its order and strictly measure.In addition, do not need to apply the device that moves it of fluid force, and keep with roughly stationary state, therefore, do not need to carry out controlling the complicated same period, and the process controlling just can to make each particle shape carrier by simple or mensuration facilitation, high precision int.
In addition, according to the present invention, use identical particle to carry out fixing, the reaction of various material and mensuration thereof etc. from start to finish, therefore, suitablely automatically carry out a series of process from start to finish.
According to the present invention, for being fixed with the multiple particle shape carriers maybe can fixing various material, the carrier maintaining part kept it, need not in advance assigned position or order, just can carry out simply importing and keeping.Therefore, easily can carry out in the place different from described carrier maintaining part waiting process, so efficient activity, the reliability of process, the certainty of process of process can be improved to fixing process of particle shape carrier self.
According to the present invention, to being fixed with the multiple particle shape carriers maybe can fixing various material, mark is carried out in advance before maintenance, this particle shape carrier is remained on optional position with roughly stationary state and measures, thus, measure the presence or absence of mark material, do not need the mensuration of carrying out careful position coordinates, therefore, mensuration is easier to.
Moreover, according to the present invention, mark can be carried out to each set with the particle shape carrier of multiple particle shape carrier.Therefore, for the particle shape carrier belonging to this set, different from the particle shape carrier for mark by making to be fixed with the particle shape carrier maybe can fixing various material, each particle shape carrier just can be made to share different functions.Therefore, by functional specialization on the particle shape carriers such as each markization, immobilization, thus more high-precision process can be carried out.
In addition, by freely setting the number belonging to the particle shape carrier of the set of described particle shape carrier, can various markization be carried out, therefore, there is extendability, diversity or popularity.
According to invention Section 2, have described carrier maintaining part can be arranged on carry out gas suction, ejection nozzle on cusp-shaped container.Therefore, controlled by the amount, speed, position, number of times, time, timing etc. using the suction of this nozzle convection cell to spray, automatically can carry out a series of process such as fixing, the transfer of various material, reaction, its mensuration from start to finish.
According to the Section 3 of invention, described cusp-shaped container is to possess: the storing section with described installation peristome and the mode being formed as the tubule thinner than storing section are formed, thus, such as, for particle shape carrier, in tubule, such as, keep in the mode being arranged in row, make each particle shape carrier be kept one-dimensionally thus, thus can measure reliably.In addition, by measuring in the mode of carrying out scanning along tubule, mensuration facilitation can be made.
Moreover, as long as imported along tubule by fluid and discharge, just can reliably carry out the contact with fluid.In addition, because tubule can insert be arranged at outside various containers, so, be applicable to the suction of liquid, discharge.In addition, according to the present invention, process under the state that can often can contact at particle shape carrier and fluid, therefore, treatment effeciency is high.
According to the Section 4 of invention, by arranging inclosure portion, can by particle shape carrier positively to enclose in described carrier maintaining part with the state that fluid can contact.Thus, particle shape carrier can not from carrier maintaining part flow out and be maintained in carrier maintaining part, and can not hinder because of the existence of particle shape carrier fluid fluidly with fluid contact.
According to Section 5 of the present invention, electric current is flowed in the entirety of wall being formed at described carrier maintaining part or the electroconductive member of a part, this electroconductive member is made to generate heat thus, by heating the particle shape carrier and fluid that are housed in described carrier maintaining part or cool, the temperature can carrying out reacting controls.
Therefore, compared with the situation of the heating arrangements such as the arranged outside well heater of the wall in carrier maintaining part, owing to being directly contact with in cusp-shaped container, therefore, the heat reflection of wall can be prevented, can further effectively to transferring heat in cusp-shaped container, the thermal efficiency is high, can carry out correct temperature and control.
Moreover due to the wall adopting electroconductive member to form carrier maintaining part, therefore, the thermal efficiency is high, do not need, at the large heating arrangement of the arranged outside derby etc. of cusp-shaped container, only to arrange its drive unit in outside.Therefore, external structure is simplified, and can reduce the scale of whole device.
Because most suitable gradient of temperature body can be arranged in each carrier maintaining part in advance, so do not need the heating arrangement meeting various condition in outer setting, there is popularity, diversity.
Because electroconductive member directly contacts with in carrier maintaining part, therefore, have high precision and loyal responsiveness, the temperature can carrying out this liquid controls.
Can shorten and apply after the heating of described liquid or cooling signal this carrier maintaining part and electroconductive member, liquid temperature reaches the time of uniform Temperature Distribution, can rapidly and effectively process.
According to Section 6 of the present invention, each set at least with the particle shape carrier of two independent particle shape carriers arranged, have fixing maybe can fix various material at least one particle shape carrier and at least one particle shape carrier to this various material maybe this set identifiably mark.Therefore, can distinguish to utilize and there is the particle shape carrier making the particle shape carrier of various substance fixed function and carry out markization, therefore, by using applicable respective different types of particle shape carrier, fixedly can to go forward side by side line identifier to material under the prerequisite keeping high reliability.In addition, in markization process, can by multiple particle shape carrier combinations together, the particle shape carrier of identifiedization of a few species therefore can be used to identify many various materials etc.
According to Section 7 of the present invention, each set at least with the particle shape carrier of two independent particle shape carriers arranged, all have at least one particle shape carrier of markization and eliminating gather between impact or determine the border particle on mutual border.Therefore, it is possible to positively carry out mark to each of each set, therefore, reliability is high.Especially, particle shape carrier arrangement is become row, in each set, when carrying out mark by making luminous intensity keep difference, by between the set that is used for adjoining by the border particle with light-proofness, the impact between adjacent set positively can be measured.
According to Section 8 of the present invention, because described particle shape carrier outside surface and keep its carrier maintaining part inwall between be formed with gap, so particle shape carrier can not hinder the flowing of fluid, the fluid imported positively can contact with particle shape carrier.Especially, by arranging protuberance at the outside surface of the particle shape carrier being held in the arrangement of at least one end in the multiple described particle shape carrier in described tubule, even if described inclosure portion has circular through hole, described particle shape carrier also can not block through hole, can not the flowing of block fluid, thus positively contact with fluid.
According to Section 9 of the present invention, the part (such as tubule) of the maintenance particle shape carrier in described carrier maintaining part, between the surface being maintained at the particle shape carrier of this carrier maintaining part and the internal face of carrier maintaining part, formation can accommodate the space of fluid, by fluid is pressed into this space for the amount (small quantity) of liquid of process, can carry out being inhaled into the contact between liquid in this carrier maintaining part and the surface integral of described particle shape carrier, thus the high process of reliability can be carried out to the liquid of small quantity.
According to Section 10 of the present invention or Section 22, for various matter retaining body, this various matter retaining body is arranged on moveable nozzle, thus, liquid can be imported in described carrier maintaining part, and liquid can be made to spray in this carrier maintaining part, therefore, it is possible to carry out the process to this various matter retaining body from start to finish.In addition, according to this device, owing to can use multiple nozzle simultaneously, therefore, it is possible to effectively process in the lump simultaneously.In addition, the process robotization from start to finish of various matter retaining body can be made.
According to Section 11 of the present invention, be arranged on nozzle by maintaining the fixing carrier maintaining part maybe can fixing the described various matter retaining body of the particle shape carrier of various material, based on the shape by described carrier maintaining part, the shape of particle shape carrier and size, fix or be suspended in the kind of the various materials on this particle shape carrier, amount of liquid, the material conditions that the coordinate position comprising the collecting position of this liquid is formed, and by the time be incubated, the treatment conditions that temperature or contents processing are formed, to the amount that the suction corresponding with this nozzle sprays, speed, number of times or position control.
Therefore, according to the present invention, use the various matter retaining bodies with the structure of regulation, simultaneously, detailed control is carried out to suction, ejection, thereby, it is possible to easily, from start to finish and have high reliability ground, rapidly and carry out efficiently on the particle shape carrier enclosed in the carrier maintaining part of this various matter retaining body fix or the process such as fixable various material reacts, stirs, cleaning.In addition, according to the present invention, controlling content by changing, just can tackle various process, therefore, there is popularity, diversity.
According to Section 12 of the present invention or Section 25, by receiving from the signal of described particle shape carrier, just can from start to finish and there is high reliability, rapidly and effectively carry out until the process that measures.
According to Section 13 of the present invention or Section 23, due to be according to the signal identified first of each kind based on the various material of identifiable design and based on imports and the second signal identified described particle shape carrier being carried out after keeping markization combine after signal carry out the method for resolving, therefore, need not withdrawn position information, just can be resolved by the identification signal information detecting peer-level, therefore, parsing is easier to.
According to Section 14 of the present invention or Section 26, for described various matter retaining body carrier maintaining part, be held in particle shape carrier wherein, by making gradient of temperature body from outside with it close to carrying out temperature control.Therefore, control with the temperature of carrying out liquid by heating the container be arranged at outside this various matter retaining body thus make compared with the situation of carrying out with the reaction of particle shape carrier, can more effectively and reliably react.
According to Section 15 of the present invention, nozzle block and independent nozzle can be made to move in the row direction in the lump, on the mobile route of described nozzle block and independent nozzle, be provided with the ranks conveying device with the transport path being provided with described row transport path and row transport path.Therefore, this conveying device can be utilized, processed by any one in nozzle block and independent nozzle, not will multiple nozzle or suck emitting mechanism be configured as line column-shaped, thus to adopt simple, the small-sized structure of minority nozzle, the various and process of complexity can just be tackled.
In addition, when carrying out suction ejection process to many handling objects, for common process item, use nozzle block to process together, and need the process item carrying out individually processing, use independent nozzle to process individually, thus, can effectively and promptly carry out various process.
Before being about to measure, adding the situation of necessary reagent when being particularly suitable for measuring individually, or before the process solely carried out by coverlet, adding the situation of the reagent kept needed for set point of temperature.
According to Section 16 of the present invention, infrared rays receiver is set by least one place on the described transport path of described ranks delivery pathways device, minority infrared rays receiver just can be used to measure successively process corresponding with each nozzle processed in multiple connected nozzle.Therefore, device can be made to simplify.Especially it is possible to utilize independent shower nozzle to be dropped into successively before by light by the reagent only needed before described infrared rays receiver is about to carry out light, thus the light effective, reliability is high can be carried out.
According to Section 17 of the present invention, by sucking to wait, particle shape carrier one by one being caught, can take out from container, transfer and to the importing of carrier maintaining part.Therefore, being suspended in liquid owing to need not make particle shape carrier but just can processing in atmosphere, therefore the manufacture of various matter retaining body is easier to.
According to Section 18 of the present invention, do not need that described particle shape carrier is floated on a liquid and just it positively can be imported and be held in described carrier maintaining part, therefore, various matter retaining body easy to manufacture, and reliability is high.
According to Section 19 of the present invention, because the carrier maintaining part resettlement section of collecting carrier maintaining part is arranged on platform, so, from importing particle shape carrier to carrier maintaining part to this carrier maintaining part to the installation of described nozzle, all need not be manual, and can carry out automatically.
According to Section 2 of the present invention, by will the multiple particle shape carriers maybe can fixing various material will be fixed with are transplanted on the position of carrier maintaining part, various matter retaining body can be manufactured.Now, how all it doesn't matter for the transfer order of the no matter set of described particle shape carrier or particle shape carrier or the position in described carrier maintaining part, and therefore, the manufacture of various matter retaining body is easier to.
According to the Section 24 of invention, in described carrier maintaining part and cusp-shaped container, be arranged on nozzle by having enclosed the various matter retaining bodies being fixed with the particle shape carrier maybe can fixing various material, based on the shape by described carrier maintaining part, the shape of particle shape carrier, fix or be suspended in the kind of the various materials on this particle shape carrier, amount of liquid, the material conditions that the coordinate position comprising the collecting position of this liquid is formed, and by the time be incubated, the treatment conditions that temperature or contents processing are formed, to the amount that the suction relative with this nozzle sprays, speed, number of times, time or position control.Therefore, according to the present invention, use the various matter retaining bodies with the structure of regulation, simultaneously, detailed control is carried out to suction, ejection, thereby, it is possible to easily, from start to finish and have high reliability ground, rapidly and carry out efficiently to be held on the particle shape carrier of this carrier maintaining part to fix or fixable various material carries out and the process such as the reaction of sucked liquid, stirring, cleaning.In addition, controlling content by changing, various process can be tackled, therefore, there is popularity, diversity.
Accompanying drawing explanation
Fig. 1 is the skeleton view of various matter retaining body in the first embodiment.
Fig. 2 is the front view of various matter retaining body in the first embodiment, cut-open view and vertical view.
Fig. 3 is the schematic diagram of the manufacturing installation representing various matter retaining body in the second embodiment.
Fig. 4 is the cut-open view representing various matter retaining body in the 3rd to the 5th embodiment.
Fig. 5 is the vertical view and the cut-open view that represent various matter retaining body in the 6th embodiment.
Fig. 6 is the cut-open view representing various matter retaining body in the 7th to the 9th embodiment.
Fig. 7 is the schematic diagram representing various matter retaining body in the tenth embodiment.
Fig. 8 is the floor map representing various matter retaining body treating apparatus entirety in the 11 embodiment.
Fig. 9 is the side view representing various matter retaining body treating apparatus in the 11 embodiment.
Figure 10 is the process flow diagram of the disposal route of various matter retaining body in the 12 embodiment.
Figure 11 is the process flow diagram of the disposal route representing various matter retaining body in the 13 embodiment.
Figure 12 is the process flow diagram of the disposal route representing various matter retaining body in the 14 embodiment.
Figure 13 is the process flow diagram of the disposal route representing various matter retaining body in the 15 embodiment.
The explanation of label
10: various matter retaining body treating apparatus
11,30,41,50,52,58,63,65,66: various matter retaining body
12,24,31,42,53,59,67: cusp-shaped container
13,32,43,54,68: extra heavy pipe
15,25,34,45,55,60,69: tubule
17: particle (particle shape carrier)
61,61a, 611a: particle assembly (set of particle shape carrier)
84: shower nozzle
103: conveying belt (ranks delivery pathways device)
106: light accepting part
Embodiment
The present invention is before importing carrier maintaining part by particle shape carrier or its set, in advance mutual discernible markization is carried out to particle shape carrier, thus, realize the efficient activity of process, in addition, the particle shape carrier imported in carrier maintaining part is remained on roughly stationary state from the measurable mode in outside, thus, realize from the sufficient reaction of various material until the robotization from start to finish of the process measured.
Then, with reference to accompanying drawing, embodiments of the present invention are described.The explanation of each embodiment, when not specifying especially, can not be interpreted as limiting content of the present invention.
Fig. 1 is the skeleton view of the various matter retaining bodies 11 representing first embodiment of the invention.This various matter retaining body 11 has the cusp-shaped container 12 as carrier maintaining part, described carrier maintaining part have as the storing section that can store liquid extra heavy pipe 13 and form thinner than this extra heavy pipe 13 tubule 15, and there is light transmission.In the upper end of this extra heavy pipe 13, there is the installation peristome 14 for being installed on the nozzle carrying out the suction of gas, the not shown of ejection.In the front end of described tubule 15, be provided with by the suction of gas, ejection and the inflow of fluid, the oral area 16 of outflow can be carried out.
In described tubule 15, the fixing biological substance maybe can fixed as number of chemical material (various material) one by one, as by the particle 17 of mutually identifiably multiple (in this example being 31) same shape (such as spherical) of mark, the particle shape carrier of formed objects, axially one by one measuring from outside along this tubule 15, and with the form trait roughly stationary state of row.Described particle 17 is before being imported in this cusp-shaped container 12, the biological substance as various material that maybe can be fixed on described particle 17 is fixed on to each, mutual identifiably setting identification key element, adopts the luminescent substance such as fluorescent material, chemiluminescent substance to carry out mark.
Releasably arrange and comprise the extra heavy pipe portion of described extra heavy pipe 13 and comprise the thin tube part of described tubule 15.With regard to described extra heavy pipe portion, with the mode that diameter is slightly less than described extra heavy pipe 13 formed this extra heavy pipe 13, with the bottom 18 of described installation peristome 14 opposition side, with regard to thin tube part, in the upside of described tubule 15, be provided with the fitting portion 15a formed in the mode that diameter is slightly larger than this tubule 15, described bottom 18 can be located in described fitting portion 15a chimericly, by making described bottom 18 carry out chimeric with described fitting portion 15a, is linked together in extra heavy pipe portion and thin tube part.
In the downside of described tubule 15, be provided with the leading section 19 of the taper in front end with described oral area 16, flow out through described oral area 16 to prevent described particle 17.
Fig. 2 (a) is the enlarged front view of the various matter retaining bodies 11 representing Fig. 1 in detail, and Fig. 2 (b) is the cut-open view observed along the direction of arrow of the AA line of Fig. 2 (a), and Fig. 2 (c) is vertical view.
As shown in Fig. 2 (a) (b) (c), be located at shown extra heavy pipe 13 downside bottom 18 bottom surface on, be provided with and there is the width less than the particle diameter of shown particle 17 or the radial opening 18a of length, therefore, described particle 17 can not be immersed in extra heavy pipe 13, and described particle 17 is enclosed in tubule 15.In addition, on the inwall of this leading section 19, be provided with along eight inwardly outstanding teat 16a of the flow direction of fluid, touch with described particle 17 with inwall and do not hinder the mode of the flowing of fluid to be provided with gap.Described opening 18a, this teat 16a and leading section 19 are equivalent to described sealing.In addition, label 14a is provided at the ridge of the outside of described installation peristome 14.The size of the various matter retaining bodies 11 of this first embodiment is that such as, the length in described extra heavy pipe portion is 1 ~ 10cm, and the length of thin tube part is 1 ~ 10cm.In addition, the particle diameter of described particle 17 is such as 0.1mm ~ 3mm, the internal diameter of described extra heavy pipe 15 or be the size that this particle can be remained row with the width in axially vertical cross section, length.
Fig. 3 represents the particle 17 of catching as described particle shape carrier and the carrier transferred catches transferred unit 20.
At this, represent described carrier catch transferred unit 20 from carrier resettlement section (not shown) catch described particle 17 and be transplanted on the various matter retaining bodies of the second embodiment cusp-shaped container 24, described particle 17 is imported and remains on the situation in this cusp-shaped container 24.
This carrier is caught the sucting (not shown) that transferred unit 20 has a breathable gas and is communicated with this sucting and utilizes the suction of described sucting can catch the tubular element 21 of described particle 17 and make described tubular element relatively-movable tubular element mobile device (not shown) between itself and the cusp-shaped container as described carrier maintaining part.
In addition, the described cusp-shaped container 24 of the second embodiment is different from the described cusp-shaped container 12 of the first embodiment, is provided with the sealing (not shown) of taper in the front end 26 of tubule 25, and the sealing handling of this taper freely.In the end of the opposition side of the described front end 26 of described tubule 25, be provided with fitting portion 25a, with the bottom 18 of chimeric extra heavy pipe 13.When being imported in this tubule 25 by described particle 17, described sealing is removed.
In addition, as shown in Figure 3, described cusp-shaped container 24 makes its front end 26 arrange upward.This cusp-shaped container 24 is supported by not shown cusp-shaped vessel leg.In addition, when the cusp-shaped container 12 for the first embodiment, described installation peristome 14 is arranged towards upside.
In addition, as shown in Figure 3, the funnelform guide 23 expanded upward is provided with in the mode of the surrounding around described front end 26.In addition, the below sucker mechanism (not shown) of suction gas also can be set, particle 17 to be located at certainly the described installation peristome of the downside of described extra heavy pipe 13, positively import in described tubule 25.
Then, Fig. 4 (a) (b) (c) represents the various matter retaining bodies 30,41,50 of the 3rd to the 5th embodiment.
Fig. 4 (a) is the diagrammatic cross-section of the various matter retaining bodies 30 representing the 3rd embodiment of the present invention.This various matter retaining body 30 have as described carrier maintaining part cusp-shaped container 31 and to be maintained in this cusp-shaped container 31 multiple (is 5 in this embodiment, for ease of observing, number is fewer than actual conditions) be fixed with the described particle 17 maybe can fixing various material.
This cusp-shaped container 31 have as described storing section extra heavy pipe 32 and form thinner than this extra heavy pipe 32 tubule 34, be the cusp-shaped container with light transmission.In the upper end of this extra heavy pipe 32, there is the installation peristome 33 for being installed on the nozzle carrying out the suction of gas, the not shown of ejection.Oral area 35 is provided with, by the suction of described gas, ejection and inflow, the outflow of fluid can be carried out in the front end of described tubule 34.Tubule 34 and extra heavy pipe 32 have the outside and inner face that are formed as roughly cylindrical shape.
In the downside slightly of the described installation peristome 33 of described extra heavy pipe 32, be provided with filtrator 38, it can make gas pass through.In addition, in the downside of this extra heavy pipe 32, utilize the roughly funnelform moving part 34a between tubule 34 and extra heavy pipe 32 to be provided with as carrier is by the thin mesh-shape component 37 of blocking portion slightly, ring 36 in side pressure thereon.In order to support described mesh-shape component 37, moving part 34a is provided with the multiple back up pads 40 being supported in described moving part 34a.Containing in this example of particle 17(as multiple particle shape carrier in described tubule 34 is 5), thereunder, as fluid by described carrier by stoping the connectivity porous member 39 of component, be installed in described tubule 34.This connectivity porous member 39 preferably utilizes the gauffer or step that are formed at tubule 34 and installs.At this, described mesh-shape component 37 and described connectivity porous member 39 are equivalent to inclosure portion.
At this, the external diameter of the particle 17 of described particle shape carrier, such as, be about 1.8mm, and the internal diameter of described tubule 34, such as, be about 2.0mm, and the length between described connectivity porous member 39 and described mesh-shape component 37, such as, be about 50mm.
In addition, when maintaining multiple particle as particle shape carrier, in order to clear and definite holding position, preferably will pay color or be held in assigned position with the particle of the coated particle shape carrier as benchmark of fluorescent material.
Around the lateral surface of described tubule 34, be there is the resistance value of regulation and to have the conductive membrane 34b of light transmission coated.By making electric current flow wherein, the temperature in tubule 34 can be made to increase.
Fig. 4 (b) is the cut-open view of the various matter retaining bodies 41 representing the 4th embodiment of the present invention.This various matter retaining body 41 have as described carrier maintaining part cusp-shaped container 42 and to be maintained in this cusp-shaped container 42 multiple (is 5 in this embodiment, for ease of observing, number is fewer than actual conditions) be fixed with the described particle 17 maybe can fixing various material.
This cusp-shaped container 42 has extra heavy pipe 43 as described storing section and the tubule 45 that formed thinner than this extra heavy pipe 43, releasably arrange relative to above-mentioned extra heavy pipe 43, is the cusp-shaped container with light transmission.In the upper end of this extra heavy pipe 43, there is the installation peristome 44 for being installed on the nozzle carrying out the suction of gas, the not shown of ejection.Be provided with oral area 46 in the front end of described tubule 45, inflow, the outflow of fluid can be carried out by the suction of described gas, ejection.In the lower end of above-mentioned extra heavy pipe 43, relative to the fitting portion 49 arranged in the mode of surrounding hole 48, can be provided with tubule 45 at its upper end, this hole 48 is arranged in the mode by its central shaft chimericly.When making the upper end of described tubule 45 be embedded in described fitting portion 49, preferably by ultrasound wave, bonding agent or thermal weld tubule 45, it is made not depart from.Described cusp-shaped container 42 is such as formed by glass, tygon, polystyrene, polypropylene etc.Tubule 45 and extra heavy pipe 43 are formed as the roughly cylindrical shape comprising inner face and outside.
In addition, contain in this tubule 45 multiple as being 5 in this example of particle 17(of particle shape carrier).In the below of its tubule 45, there is aperture or the space of the size degree passed through that can stop described particle 17, the mode in the hole passed through of fluid will be hindered to be provided with the teat 47 outstanding to its radial direction because of the existence of described particle 17 to be formed.In addition, the size being arranged on the described teat 47 of the lower end of described tubule 45 is the size passed through stoping described particle 17.This particle 17, such as, formed by water-absorbing material, Porous plastics, resin etc.Described hole 48 and teat 47 are equivalent to described inclosure portion.
At this, such as, the external diameter of described tubule is about 2.5mm, and internal diameter is about 2mm.In addition, the external diameter of described fitting portion 49 is about 5mm, and its internal diameter is consistent with the external diameter of described tubule.In addition, described teat 47 is to the length in described hole 48, and be such as about 50mm, the aperture in described hole 48 not by being advisable, such as, is about 1mm with described particle 17, and the length of described extra heavy pipe 43, such as, be about 50mm.
Fig. 4 (c) is the cut-open view of the various matter retaining bodies 50 representing the 5th embodiment of the present invention.This various matter retaining body 50 is different from the various matter retaining bodies 41 of the 4th embodiment shown in Fig. 4 (b), and it adopts the irregular particle of surperficial tool 51 to replace enclosing the particle 17 being positioned at lower side in the particle 17 in described tubule 45.Thereby, it is possible to prevent described particle 17 to be close contact in described teat 47 and hinder the state of affairs of the flowing of fluid.
Fig. 5 is the diagrammatic cross-section of the various matter retaining bodies 52 representing the 6th embodiment.Fig. 5 (a) is the sectional view that the AA line of Fig. 5 (b) is observed.This various matter retaining body 52 has to be fixed with as the cusp-shaped container 53 of described carrier maintaining part and multiple (being 15 in this embodiment) be maintained in this cusp-shaped container 53 maybe can fix various material and the described particle 17 having carried out mutually identifiably mark by identification elements such as fluorescent materials.The fitting portion 55a that described cusp-shaped container 53 has the bottom of the extra heavy pipe 54 be installed on as described storing section and the tubule 55 being formed thinner than the cylindrical portions of described extra heavy pipe 54 are the cusp-shaped containers with light transmission.In the upper end of this extra heavy pipe 54, there is the installation peristome for being installed on the nozzle carrying out the suction of gas, the not shown of ejection.The leading section 56a of described tubule 55 is taper, is provided with oral area 56 in front end, can stop the discharge of described particle 17, meanwhile, can be carried out inflow, the outflow of fluid by the suction of described gas, ejection.In addition, at the lower bottom part of described extra heavy pipe 54, be provided with and there is the length less than the particle diameter of described particle 17 or the radial opening 54a of width.Described opening 54a and leading section 56a is equivalent to described inclosure portion.Radial opening 54a, the structure such as had is: central part has plectane, and it supports with the rod of radiated entends by inner peripheral surface.
In addition, on the inwall of this tubule 55, to by outstanding for separated direction between described oral area 56 and described installation peristome and be axially arranged with four ridges 57 along what link this oral area 56 and described installation peristome.By arranging this ridge 57, in the tubule 55 of cylindrical shape, particle 17 is by described oral area 56, and the smooth fluid ground flowing flow out, flowed into, positively can carry out the contact between fluid and described each particle 17.
Fig. 6 is the sectional view of the various matter retaining bodies 58,63,65 of the 7th to the 9th embodiment.
The various matter retaining bodies 58 of the 7th embodiment shown in Fig. 6 (a), have as the cusp-shaped container 59 of described carrier maintaining part, maintain in this cusp-shaped container 59 many groups (being 8 groups in this embodiment) as the particle assembly 61 of the set of particle shape carrier, be fixed with in each particle assembly 61 and maybe can fix various material, and such as carried out mutually the described particle 17 of identifiably mark with fluorescent material and covered the covering with particle 62 as border particle of the light from described fluorescent material in the mode that can not arrive adjacent particle assembly 61.This covers with particle 62 also can be opaque particle, such as, have the resin-made particles such as metal particle, plastics.The fitting portion 60a that described cusp-shaped container 59 has the bottom of the extra heavy pipe 54 be installed on as base storing section and the tubule 60 being formed thinner than the cylindrical portions of described extra heavy pipe 54 are the cusp-shaped containers with light transmission.In the upper end of this extra heavy pipe 54, there is the installation peristome for being installed on the nozzle carrying out the suction of gas, the not shown of ejection.
The inner face of described tubule 60, such as, formed prismatic, and under the state that inside maintains particle 17 grade, liquid also can utilize nozzle to the suction of gas, ejection and flowing swimmingly along tubule 60.The leading section 60c of described tubule 60 is formed as taper, is provided with oral area 60b in its front end, can stop the discharge of described particle 17, meanwhile, can be carried out inflow, the outflow of fluid by the suction of described gas, ejection.In addition, at the lower bottom part of described extra heavy pipe 54, be provided with the radial opening 54a with the internal diameter less than the particle diameter of described particle 17.Described leading section 60c and opening 54a is equivalent to inclosure portion.
The various matter retaining bodies 63 of the 8th embodiment shown in Fig. 6 (b), have as the cusp-shaped container 59 of described carrier maintaining part, in this cusp-shaped container 59, maintain many groups (being 8 groups in this embodiment) each particle assembly 61a ~ 61h as the set of particle shape carrier.In each particle assembly 61a ~ 61h, there is the reaction particle 17a ~ 17h as particle shape carrier respectively that be fixed with the mutually different biological substance maybe can fixed as various material, meanwhile, have respectively be fixed with the mark material that mutually can identify these various materials as any one in the mark particle 641 ~ 648 of particle shape carrier.
The various matter retaining bodies 65 of the 9th embodiment shown in Fig. 6 (c), have as described carrier maintaining part cusp-shaped container 59, remain on many groups (being 5 groups in this embodiment) in this cusp-shaped container 59 each particle assembly 611a ~ 611e as the set of particle shape carrier.In each particle assembly 611a ~ 611e, there is the reaction particle 17a ~ 17e as particle shape carrier respectively that be fixed with the mutually different biological substance maybe can fixed as various material, meanwhile, have respectively be fixed with the mark material that mutually can identify these various materials as any one in the mark particle 641 ~ 644 of particle shape carrier.But different from the situation of the various matter retaining bodies 63 of the 8th embodiment, the number belonging to the particle shape carrier of each particle assembly 611a ~ 611e is different, has deviation.In addition, the number (4) of mark particle 641 ~ 644 identifies mutually by the number that the group number (5 groups) than the particle assembly 611a ~ 611e for identifying is little.
In addition, in each set, covering with also different in particle 62 this point as border particle is provided with.
Fig. 7 is the skeleton view of the various matter retaining bodies 66 representing the tenth embodiment, and this various matter retaining body 66 has maybe can be fixed various material as the cusp-shaped container 67 of described carrier maintaining part, multiple being fixed with remained in this cusp-shaped container 67 and having carried out the described particle 17 of mutual identifiably mark with fluorescent material etc.The fitting portion 69a that described cusp-shaped container 67 has the bottom of the extra heavy pipe 68 be arranged on as described storing section and the tubule 69 being formed thinner than the cylindrical portions of described extra heavy pipe 68 are the cusp-shaped containers with light transmission.In the upper end of this extra heavy pipe 68, there is the installation peristome (not shown) for being installed on the nozzle carrying out the suction of gas, the not shown of ejection.
As shown in Figure 7, described tubule 69 has: be installed on the fitting portion 69a of the bottom of shown extra heavy pipe 68, be arranged at the downside of this fitting portion 69a to be arranged to spiral helicine spire 69b around the mode linking the installation peristome of described extra heavy pipe 68 and the axial rotation of oral area 70 and to be arranged to linearity and the leading section with oral area 70 is formed as the line part 69c of taper can insert mode in various container along described axis.Described particle 17 is held in described tubule 69.According to the various matter retaining bodies 66 of this embodiment, because tubule 69 has the spire 69b be arranged in the mode spirally rotated around axle, therefore, it is possible to many particle shape single compact are kept, thus space-saving and there is rigidity.In addition, accept the light from particle 17 in the mode scanned along tubule 69, mensuration is easier to.
Fig. 8 represents the floor map of the entirety of the various matter treating devices 10 of eleventh embodiment of the invention.
This various matter treating device 10 comprises: various matter retaining body treating apparatus 80, and it has suction emitting mechanism, is arranged on nozzle by described various matter retaining body 11, thus sucks this various matter retaining body 11, spray process; Various material keeps processing region 81, suspending liquid containing various subject or reagent etc. sucks or sprays for passing through by it in described various matter retaining body 11, carry out the suction of the suspending liquid to described particle 17, ejection, externally the dispensing, stirring, cleaning, extraction, transfer, reaction etc. of container; Reagent dispensing region 82, its nozzle had for utilizing described various matter retaining body treating apparatus 80, is dispensed in the cusp-shaped container 12 of described various matter retaining body 11 by the reagent measuring use etc.; Measure region 83, it obtains the optical information for implementing to measure to the particle 17 enclosed in described various matter retaining body 11.
Described various matter retaining body treating apparatus 80 shown in Fig. 8, Fig. 9 utilize the nozzle be communicated with suction emitting mechanism to carry out suction, the ejection of gas.This various matter retaining body treating apparatus 80 has the shower nozzle 84 of nozzle 117 that be arranged in column direction (longitudinal direction in drawing), that have multiple be connected (in this example being nine to be connected), and sucks simultaneously this shower nozzle 84, spray.In addition, the nozzle 117 being positioned at termination in nine connected nozzles 117 is single nozzles, its position, as shown in (position of the label 112b of Fig. 8), is set to leave slightly the position (position of the label 112a of Fig. 8) of eight connected nozzle 117, i.e. nozzle block.
As shown in Figure 9, in described suction emitting mechanism, there is the large diameter part 116 on the top being slightly arranged at described each nozzle 117 and the plunger rod 112 for making plunger 115a slide in the cylinder 115 linked with this each nozzle 117.In addition, the mounting means of nine described plunger rods 112 is: be located at nine concave parts at edge of the drive plate 123 that can simultaneously move up and down, there is the diameter separately larger than the diameter of this plunger rod 112, and end 112a and the end 112b that eight that give prominence to oriented radial direction connected.In addition, described shower nozzle 84 in the row direction (transverse direction on drawing or left and right directions) move simultaneously.
In addition, as shown in Figure 9, this drive plate 123 with and the nut portions 113 that screws togather of ball screw 114 link.Described each plunger rod 112 is exerted a force downwards often by the spring be located on described cylinder 115.Therefore, described each plunger rod 112, when moving up, rises by the power of described each nut portions 113, and when moving down, not by the effect of this nut portions 113, declines due to described spring force.This each ball screw 114 utilizes the motor 110 be located on supporting member 111 that cross section is コ font drive and rotate, and thus, described drive plate 123 and nine described plunger rods 112 move up and down in the lump.
In addition, in nine connected nozzles 117, because described single nozzles is located on described shower nozzle 84, therefore, carry out sucking, spraying together with other eight connected nozzle block, in addition, the lifting of elevating mechanism is also carried out with move horizontally (left and right directions of Fig. 8) of line direction simultaneously.But this single nozzles may be used in described reagent dispensing region 82, the reagent that dispensing measures in described various matter retaining body 11.When using this single nozzles, for various matter retaining body is by the state removed from other nozzle block.In addition, when using nozzle block, this single nozzles is in the state of not installing described cusp-shaped container etc.
In fig .9, in basket 87, the nut portions 120 there is ball screw 119, screwing togather with this ball screw 119 and be arranged in this nut portions 120, that one end has described supporting member 111 supporter 121.In addition, on this basket 87, be provided with the motor 88 of ball screw 119 described in rotary actuation.By the structure of motivation be up and down made up of these components, described nozzle 117 can move up and down.
Gradient of temperature device 71 is provided with in the below of basket 87.This gradient of temperature device 71 is based on as nine the described various matter retaining bodies 11 be installed on nine connected nozzles, comprise: formed along column direction close to the mode that maybe can contact such height and width with tubule 15 to have, and inside has the heated wall 72 of well heater; Be arranged in this heated wall 72, there are in the inside projecting in the mode of clamping described each tip from both sides 10 pieces of heating plates 73 of well heater.Heated wall 72 is preferably formed the shape of coincideing with the shape of the tip as controlled target temperature.At this, described heated wall 72 and heating plate 73 are equivalent to described gradient of temperature body.
This gradient of temperature device 71 comprises: motor 74, its be arranged on described various matter retaining bodies 11 on the described nozzle 117 of described shower nozzle 84 near to or in contact with, can heat this tip; By the ball screw 76a of this motor 74 rotary actuation; The nut portions 75 screwed togather with this ball screw 76a; Link with this nut portions 75, along scheming the movement bar 76b that upper left and right directions is removable, link described heated wall 72 and heating plate 73.
In the downside of this gradient of temperature device 71, there is pawl 122a and nine piece of magnetite 122b of comb teeth-shaped; Along the motor 89 that the upper left and right directions of figure moves, can remove the described various matter retaining bodies 11 be arranged on described nozzle 117, maybe can bring magnetic field; Can the movement back up pad 90 of movement in left-right direction by the driving of this motor 89; And be arranged on this and move with movement bar 91a, the 91b in back up pad 90.
In addition, this various matter retaining body treating apparatus 80 is arranged in the mode hung down from upside, and in the mode in the whole region and other essential regions that cover described various matter treating device 10, be placed through and utilize the X-axis of not shown straight-moving mechanism (line direction) travel mechanism to move.
In addition, then see Fig. 8, in described various matter retaining body processing region 81, have: box type container 92, its well (well) having eight of suspending liquid that collecting subject suspends connected arranges 92a; Matrix form container 95, it is made up of the well row 79 with the tubule of accommodating various matter retaining body, the wells of 6 row × 8 row of well row 97 of accommodating the target substance or particle shape carrier such as reaction particle, mark particle that extract from various product or subject or covering the thin tube part having the tubule of various matter retaining body 11 with the well row 96,99 of particle etc. and collecting or the extra heavy pipe portion with the extra heavy pipe being arranged on this thin tube part; Eight box type containers 100, its for accommodate implement this process and need various reagent, various fluorescent material and material or process product, and have can the well 100a ~ 100l of pre-packaged.In this box type container 100, label 100k, 100l represent the pre-incubation well and insulation well that are provided with hot-zone respectively.In addition, described nozzle 117 also can be formed as, and described tubular element 21 is freely installed in handling, and can catch, transfers particle 17.
In addition, on the well row 92a of the described object materials such as collecting subject, respectively carry the bar code 92b of display about the information of its object material.This bar code 92b is read by bar code reading part 93 motion scan reading bar code 92b.Label 93a is the travel mechanism driving this bar code reading part 93.
Described eight connected nozzle 117(nozzle block at described various matter retaining body treating apparatus 80) mobile route on, conveyer 103 is provided with in the mode of the surrounding surrounding eight connected described box type containers 100, it can move along prismatic transport path, this prismatic transport path has along column direction (longitudinal direction drawing on parallel with the orientation of eight connected nozzles, Y-direction) row transport path 103a, 103c, and along a described nozzle 117(single nozzles) mobile route on line direction (laterally, X-direction) row transport path 103b.
This conveyer 103 is equivalent to described ranks delivery pathways device, its with and described nozzle between the consistent mode in interval be provided with 32 tip resettlement sections (or pipe) 102 altogether, and these tip resettlement sections 102 link movably with this conveyer 103.Therefore, the position shown in Fig. 8, utilizes the nozzle 117 that eight of described various matter retaining body treating apparatus 80 connected, and to being arranged in row transport path 103a, suction, the ejection of liquid can be carried out in 102 groups, two row tip resettlement section on 103c.In addition, utilize the described nozzle 117(single nozzles be provided separately with described eight nozzle groups be connected of the described nozzle block of described various matter retaining body treating apparatus 80), can to the following row transport path 103b be arranged in as described ranks delivery pathways device in square transport path, namely the selected tip resettlement section (or pipe) 102 in described reagent dispensing region 82 is positioned at, according to object dispensing reagent, such as chemiluminescent matrix liquid etc.Especially, in the PCR pre-treatment when being about to carry out DNA and extracting, before PCR reactant liquor etc. is about to reaction, dispensing is carried out.
And, in described mensuration region 83, in the square transport path of described ranks delivery pathways device, be provided with measuring point 104, at this measuring point 104, utilize and trigger light source 105 to described various matter retaining body 11 internal radiation exciting light, accept at light accepting part 106 light that sends and measure.Thereby, it is possible to process according to processing intent each various matter retaining body 11.
In addition, although not shown, but in order to control these various matter treating devices 10, have for inputting the input media of instruction that user sends or data, carrying out the signal conditioning package such as CPU, display device, various storer, communicator of the process such as various computings, instruction is performed to the suction emitting mechanism of described various matter retaining body treating apparatus 80, travel mechanism, ranks delivery pathways device and the device etc. measured in region 83, or reception is from the signal of these devices.In this signal conditioning package, be provided with control part, this control part based on by described nozzle, be arranged on material conditions and contents processing that component on nozzle or the structure of various matter retaining body, the kind of the material be present in fluid, concentration, the amount of fluid, the temperature of fluid or carrier or the coordinate position of collecting position that comprises this fluid form, the amount of the suction of described nozzle or ejection, speed, number of times, time or position are controlled.
Then, as the various matter retaining body disposal routes of the 12 embodiment, based on Figure 10, illustrating the mono-base of the SNPs(of DNA many types of) somatotype uses the example of described various matter retaining body 30.
Multiple SNP positions that will measure, will have four kinds of oligomerization nucleotides of base sequence of the possibility that there is hybridization as checking matter, and on four that often kind of ground is fixed in multiple (in this example being 5) described particle 17 respectively.In order to be fixed on particle 17, in advance described particle 17 Surface Creation or manifest functional group, make it be combined with described checking matter, then use suitable solvent that surface clean is clean.
Such as, in SNP1(primary importance), there is the possibility of base T or base C two profiles state, in the SNP2(second place), there is the possibility of bases G or base A two profiles state.Be base T, C, G, A tetra-kinds.
To the particle 17 of the base sequence of the T be fixed with for judging SNP1, be fixed with the particle 17 of the base sequence of the C for judging SNP1, be fixed with the particle 17 of the base sequence of the G for judging SNP2, the particle 17 being fixed with the base sequence of the A for judging SNP2 sets mutual discernible identification elements, from four kinds of fluorescent materials of regulation, such as FITC(fluorescein, isothiocyanates), rhodamine, isothiocyanate, IRD40, the organic substances such as CY3 or CY5, or europium complex etc. sends in the dead matter of life-span long fluorescence and selects four kinds of different fluorescent materials, in mutual discernible mode, mark is carried out to the described particle 17 being fixed with four kinds of different base sequences respectively.At this, for making between each particle 17 mutually to identify and light that the fluorescent material that uses sends is equivalent to the signal that identifies based on described first.
As shown in Figure 10 (a) shows, in the described tubule 34 of eight with light transmission described cusp-shaped containers 31, connectivity porous member 39 is set, there is no base sequence at random or according to arbitrary order one of them particle 17 of five particle 17(added containing the described particle 17 being fixed with described base sequence and fluorescent material, identifiedization is not had) yet, mesh-shape component 37 be set and enclosed, thus, forming eight various matter retaining bodies 30.
Such as, about the situation of eight experimenters, the situation of the SNPs somatotype position simultaneously determining many places (being two places in this example) is respectively described.In this case, in step sl, on the installation peristome 33 of upper end being located at described extra heavy pipe 32, eight of above-mentioned formation various matter retaining bodies 30 are arranged on respectively on the connected described nozzle 117 of eight of described various matter retaining body treating apparatus 80.
On the other hand, be located at described various matter retaining body processing region 81, collecting eight subjects well row 92a in, accommodate following subject.Namely, genome is extracted respectively from the blood of eight experimenters, utilize thermo cycler (サ mono-マ Le サ イ Network ラ mono-) by these genomes, increase containing the fragment of SNPs somatotype position described in many places, then, with the material of fluorescent material generating identification, eight described subjects of each for correspondence experimenter are housed in described well row 92a respectively.In addition, in described eight connected box type containers 100, BW damping fluid is housed in well 100a ~ 100c wherein.
In step s 2, as shown in Figure 10 (b), by mobile device, the described shower nozzle 84 of described various matter retaining body treating apparatus 80 is advanced in the row direction, eight described tubules 34 are inserted simultaneously in these well row 92a, suck the suspending liquid in described well row 92a, and be full of in described tubule 34 simultaneously.
In step s3, as shown in Figure 10 (c), with fixing speed s1(such as about 200 microlitres/second), amount V1(such as about 400 microlitres), repeatedly carry out such as 10 times via described nozzle and suck ejection, stir thus, thus the multiple described particle 17 in described tubule 34 is fully contacted with described suspending liquid.Now, in order to promote reaction, rated current is flowed in described conductive membrane 34b, to carry out temperature control.
So, in step s 4 which, as shown in Figure 10 (d), combined by the hybridization described particle 17 corresponding to each position of described SNP by the DNA fragmentation of the fluorescent material markization in described suspending liquid.Raffinate is discharged in described well row 92a.At this, for the described four kinds of different types of fluorescent materials of fluorescent material by the fluorescent material of this DNA fragmentation markization being be used for identifying the base sequence be fixed on each particle 17.Signal from this fluorescent material is equivalent to the described signal based on the second mark.
In step s 5, as shown in Figure 10 (e), described various matter retaining body treating apparatus 80, to the described various matter retaining bodies 30 reacting the described particle 17 terminated enclosed be transplanted on the position of the well 100a of described eight connected box type containers 100, for described BW damping fluid, such as, with fixing speed s2(such as about 760 microlitres/second to about 1700 microlitres/second), small quantity V2, such as several tens of microliters ~ hundreds of microlitre (such as about 500 microlitres), repeatedly carry out such as 10 times and suck ejection, clean thus.In addition, repeatedly same operation is carried out to well 100b, 100c.
In step s 6, as shown in Figure 10 (f), described shower nozzle 84 is moved to the position of the tip resettlement section (or pipe) 102 at the row transport path 103a place stopping at described conveyer 103 by the described various matter retaining bodies 30 after cleaning terminates, described pawl 122a is utilized to throw off from the multiple nozzle block (117) be arranged on this shower nozzle 84 and accommodated by this tip resettlement section 102, drive described conveyer 103, carry along described transport path.When this tip resettlement section 102 arrives described row transport path 103b, the mode of coming the position containing point head 78 with described single nozzles (117) makes shower nozzle 84 move integrally, decline, thus, head 78 will be divided only to be arranged on this single nozzles, then, move to described reagent resettlement section 77 and suck predetermined reagent, afterwards, along described row transport path 103b using measure reagent such as the reagent of described regulation, from the installation peristome 33 of the various matter retaining body 30 of selected conveying, be dispensed in eight each tip resettlement sections 102 of stopping.Afterwards, drive this conveyer 103 and be transported to the measuring point 104 be located on this transport path, irradiating exciting light at this measuring point 104, accepting the light in described tubule 34 by light accepting part 106.Now, by measuring the combination based on the signal of the first mark and the signal based on the second mark, the structure elucidation of described target substance is carried out.
Secondly, with reference to Figure 11, using the allergy inspection of the parsing example as protein, the various matter retaining body treatment steps of the 13 embodiment when use described various matter retaining body 50 are described.
Will from various allergin such as, Chinese fir pollen, pig dish, mite, mould in four kinds of materials obtaining, be respectively fixed on four particles 17.In order to described allergin is fixed on particle 17, in advance described particle 17 Surface Creation or manifest functional group.The particle 17 of these four kinds of allergins will be fixed with respectively as identification elements, with discernible four kinds of different fluorescent materials mutually, such as, select from fluorescent material as above, carry out mark in mutual discernible mode.At this, from the light of the fluorescent material for making mutual identification between each particle 17 use, be equivalent to the signal based on the first mark.
As shown in Figure 11 (a) shows, in step s 11, in eight described well row 99, contain each tubule 45 with eight described cusp-shaped containers 42 of light transmission shown in Fig. 4 (c), irregular for tool particle 51 is put into each tubule 45 in advance.Then, random or add four particles 17 comprising the particle 17 being fixed with described allergin and fluorescent material respectively with random order, finally, described tubule 45 is being housed in the installation peristome 44 of upper end of described extra heavy pipe 43 in the extra heavy pipe portion that is located at of described well row 97, be installed on described nozzle 117 also mobile, this fitting portion 49 is pressed into described tubule 45, make tubule 45 chimeric with this fitting portion 49, then, utilize ultrasound wave or heating to carry out welding etc. and carry out installing and sealing, thus form eight various matter retaining bodies 50.
On the other hand, be located at described various matter retaining body processing region 81, in the well row 92a that accommodates described subject, contain and gather from eight experimenters the serum come; In each well 100a of eight connected box type containers 100, contain the BSA solution that TBS damping fluid 50mM, pH are 8 1%; In well 100b ~ 100f, contain by TBS damping fluid 50mM and pH the cleaning fluid of the Tween solution composition being 8 0.005%; In well 100g, contain and identified by fluorescent material the suspending liquid being suspended with antihuman IgE antibody changed.In addition, described antihuman IgE antibody is carried out to the fluorescent material of markization, use with for identifying that described four kinds of different types of fluorescent materials of fluorescent material of the allergin being fixed on each particle 17 carry out.Signal from this fluorescent material is equivalent to the described signal based on the second mark.
In this stage, described shower nozzle 84 is moved to the position of the tip resettlement section 102 at the row transport path 103a place stopping at described conveyer 103, described pawl 122a is utilized to make described various matter retaining body 50 throw off from eight that are arranged on this shower nozzle 84 connected nozzle block (117) and be accommodated in this tip resettlement section 102 being arranged in described row transport path 103a, drive described conveyer 103, carry along described transport path.When this tip resettlement section 102 arrives described row transport path 103b, described single nozzles (117) is moved to the reagent resettlement section 77 of accommodating described predetermined reagent, if desired, then suck described predetermined reagent, afterwards, move to selected described various matter retaining bodies 50 along described row transport path 103b, described mensuration reagent is dispensed in eight each tip resettlement sections 102 of stopping from the installation peristome 44 of this various matter retaining body 50.Afterwards, the measuring point 104 be located on described transport path, accepts the light from this particle 17 at described light accepting part 106 and measures.Thereby, it is possible to according to each particle 17 of Signal analysis based on the first mark, the identification information of each particle 17 can be read.This identification information is stored in the storer as control part.
In step s 12, as shown in Figure 11 (a) (b) (c), be contained in the solution of well 100a to measure v3(such as about 500 microlitres), speed s3(such as about 760 microlitres/second) carry out suction ejection, thus this solution is stirred, the surface of described particle 17 is interdicted.
In step s 13, as shown in Figure 11 (d), utilization TBS buffer solution 50mM, pH be housed in the well 100b of described box type container 100 is that the Tween solution of 8 0.005% cleans.Then, in step S14, as shown in Figure 11 (e), the described various matter retaining bodies 50 be arranged on described nozzle are moved to the described well row 92a of collecting subject, the serum be housed in these well row 92a to be sucked in described tubule 45 and to make it contact with subject, in this tubule 45, under about 37 degree, the IgE antibody in serum and described allergin is made to react 30 minutes.Now, temperature constant state is remained in order to make this tubule 45, to clamp the mode of this tubule 45 from both sides, heated wall 72 that make described gradient of temperature device 71, that clip setting with the heating plate 73 of comb teeth-shaped arrangement heats close to described eight connected various matter retaining bodies 50.Thereby, it is possible to effectively, positively heat in tubule 45.
Then, in step S15, as shown in Figure 11 (f), this various matter retaining body 50 is transplanted in the well 700c of described box type container 100.In this well 100c, contain described cleaning fluid, such as, with speed s4(such as about 760 microlitres/second ~ 1700 microlitres/second), amount v4(such as about 500 microlitres) repeatedly carry out such as 10 times and suck ejection, clean thus.Further, described various matter retaining body 41 is transplanted on well 100d, and repeatedly cleans.
Then, in step s 16, as shown in Figure 11 (g), described shower nozzle 84 is transplanted on described well 100g, carry out reacting to identify the antihuman IgE antibody changed with the fluorescent material be housed in this well 100g and suck this suspending liquid and make it contact with described particle 17, at 37 DEG C, maintain 30 minutes.Now, also as mentioned above, make the heated wall 72 of gradient of temperature device 71 close to described various matter retaining body 50, heat in this tubule 45 thus.
In step S17, as shown in Figure 11 (h), be transplanted on the well 100e of described box type container 100, to accommodated cleaning fluid, such as with speed s5(such as about 760 microlitres/second ~ about 1700 microlitres/second), amount v5(such as about 500 microlitres) carry out about 10 times and suck ejection, thus described particle 17 is cleaned.Move to well 100f and repeatedly carry out identical operation.
Then, in step S18, as Figure 11 (i) shown in, described shower nozzle 84 is moved to the tip resettlement section 102 at the described row transport path 103a place stopping at described conveyer 103, utilize described pawl 122a that described various matter retaining body 50 is thrown off from eight that are arranged on this shower nozzle 84 connected nozzle block (117) and this tip resettlement section 102 of being arranged on described row transport path 103a is accommodated, drive described conveyer 103, carry along described transport path.When this tip resettlement section 102 arrives described row transport path 103b, described single nozzles 117 is moved to the reagent resettlement section 77 of accommodating described predetermined reagent, and suck predetermined reagent, afterwards, move to selected described various matter retaining bodies 50 along described row transport path 103b, described mensuration reagent is dispensed in eight each tip resettlement sections 102 of stopping from the installation peristome 44 of this various matter retaining body 50.Then, be located at the described measuring point 104 on described transport path, accepting the light from this particle 17 at described light accepting part 106 and measure.Now, by the identification information of each particle 17 that obtained by the signal based on the first mark with by the signal combination identified based on second, can carry out specific to reacted allergin.
With reference to Figure 12, resolve example with the protein securing protein, the various matter retaining body disposal routes of the 14 embodiment when use described various matter retaining body 41 are described.In this process, in fig. 12 (a), by there is multiple (in this example being 5 kinds) for the base sequence of marking protein and the oligonucleotide of protein capture material of catching expressed protein, be separately fixed on the particle 17 shown in Fig. 4 (b).Then, as identification elements, use discernible five kinds of different types of fluorescent materials mutually, such as selecting from fluorescent material as above, further mark being carried out to the particle 17 of the base sequence be fixed with respectively for expressing above-mentioned five kinds of protein in mutual discernible mode.At this, from the light of the fluorescent material for making mutual identification between each particle 17 use, be equivalent to the signal based on the first mark.In order to fix these materials, in advance described particle 17 Surface Creation or manifest functional group.Thus, to expressed protein expression amount, check with the associativity of specific protein.In this example, by 17 random or be contained in each tubule 45 of eight described cusp-shaped containers 42 with random order in five kinds of described examples, the tubule 45 containing this particle 17 is carried out chimeric with the fitting portion 49 of the lower end being located at described extra heavy pipe 43, and installed by bonding or welding, enclose therefrom, thus form eight described various matter retaining bodies 41.
On the other hand, be located at Fig. 8 described various matter retaining body processing regions 81, in each liquid storage portion 100a of eight connected box type containers 100, contain the solution of amino acid, ribosomes etc.; In liquid storage portion 100b ~ 100g, contain by PBS damping fluid, as surfactant 0.05% the cleaning fluid (being later called " PBS-T ") that forms of Tween20 damping fluid; In liquid storage portion 100h, contain the suspending liquid of the skimmed milk being suspended with 5% in PBS-T; In liquid storage portion 100i, the antibody contained by chemiluminescent substance qualitative character, the solution of biotinylation material.In addition, this chemiluminescent substance for mark is certainly different from for identifying described five kinds of fluorescent materials of the base sequence be fixed on each particle 17.Signal from this chemiluminescent substance is equivalent to the described signal based on the second mark.
In the step s 21, by the various matter retaining bodies 41 formed like this, be installed at the installation peristome 44 of the upper end being located at its extra heavy pipe 43 on the described nozzle 117 of described various matter retaining body treating apparatus 80.Then, as shown in Figure 12 (a) (b) (c), eight of the described shower nozzle 84 of described various matter retaining body treating apparatus 80 connected nozzles 117 are moved to together the liquid storage portion 100a of described box type container 100, and will the solution such as the described amino acid of this liquid storage portion 100a be contained in, with speed s6(such as about 200 microlitres/second), amount v6(such as about 500 microlitres) suck in described tubule 45.In this condition, such as to clamp the mode of this tubule 45 from both sides, heated wall 72 that make described gradient of temperature device 71, that clip setting with the heating plate 73 of comb teeth-shaped arrangement close to described eight connected various matter retaining bodies 41, thus heats in this tubule 45.Thereby, it is possible to effectively, positively heat in tubule 45, and maintain 1 hour under 37 degree.
In step S22, as shown in Figure 12 (d), after described liquid is sprayed from described tubule 45, described shower nozzle 84 is made to move to liquid storage portion 100b, by described PBS-T solution to described tubule 45 with speed s7(such as about 760 microlitres/second ~ about 1700 microlitres/second), amount v7(such as about 500 microlitres) repeatedly carry out such as 10 times and suck ejection, clean thus.Also repeatedly this operation is carried out at liquid storage portion 100c.
In step S23, as shown in Figure 12 (e), make described shower nozzle 84 move to liquid storage portion 100h, and suck the skimmed milk suspending liquid of described PBS-T and 5%, react 1 hour under room temperature state, thus, interdict.
In step s 24 which, as shown in Figure 12 (f), after described liquid is sprayed from described tubule 45, described shower nozzle 84 is made to move to liquid storage portion 100d, by described PBS-T solution to described tubule 45 with speed s8(such as about 760 microlitres/second ~ about 1700 microlitres/second), amount v8(such as about 500 microlitres) repeatedly carry out such as 10 times and suck ejection, clean thus.Also repeatedly this operation is carried out at liquid storage portion 100e.
In step s 25, as shown in Figure 12 (g), described various matter retaining body 41 is transplanted on liquid storage portion 100i, the described suspending liquid being suspended with antibody, biotinylation material sucked by described chemiluminescent substance qualitative character, afterwards, about 30 minutes ~ about 1 hour is at room temperature incubated.
Then, in step S26, as shown in Figure 12 (h), be transplanted on liquid storage portion 100f, described PBS-T solution carried out such as 10 times to described tubule 45 repeatedly with speed s3 and sucks ejection, clean thus.Also repeatedly this operation is carried out at liquid storage portion 100g.
In step s 27, as Figure 12 (i) shown in, described shower nozzle 84 is moved to the position of the tip resettlement section 102 at the row transport path 103a place stopping at described conveyer 103, described pawl 122a is utilized to make described various matter retaining body 41 throw off from multiple (eight the connected) nozzle block (117) be arranged on this shower nozzle 84 and be accommodated in this tip resettlement section 102 being arranged in described row transport path 103a, drive described conveyer 103, carry along described transport path.When this tip resettlement section 102 arrives the position of described row transport path 103b, described single nozzles 117 is moved to described reagent resettlement section 77, and suck described predetermined reagent, afterwards, move to selected described various matter retaining bodies 41 along described row transport path 103b, chemiluminescence matrix liquid is dispensed in eight each tip resettlement sections 102 of stopping as predetermined reagent from the installation peristome 44 of this various matter retaining body 41.Afterwards, the measuring point 104 be located on described transport path, accepts the light from this particle 17 at described light accepting part 106 and measures.Now, in order to accept the signal based on the first mark, the excitation light pulse of the respective wavelength from described triggering light source 105 is located at open mode, each each particle 17 is irradiated, light is accepted, based on the intensity of the signal of the second mark during by repeatedly opening, closing ripple control to each of each particle to be determined at this pulse be closed condition at light accepting part 10.According to the intensity based on this first signal identified and the described signal based on the second mark, to carrying out specific with the reacted protein such as antibody, biotinylation material by described chemiluminescent substance qualitative character, or according to its intensity, its expression can be measured.
Then, with reference to Figure 13, the situation disposal route of the various matter retaining bodies by the 15 embodiment being applied to SNPs detection reaction is described.
As illustrated shown in Figure 13, the method is applicable to each SNPs(Single Nucleotide Polmorprphysms everywhere to the subject gene (ATase exon6, ATase exon8, CYP2C19 exon5, CYP2D6 exon1) gathered from eight experimenters) process that detects of the base of many types of (in this case two kinds).This process comprises: as the test portion preparation process S31 of preparatory stage, extracted by subject gene and increase, by ASPE method preparation ASPE product described later; Enclose operation S32, the probe of detection and the particle of tagDNA described later in the tubule 15 of cusp-shaped container 12 should enclosing described various matter retaining body 11 are combined, prepare multiple (in this example being 8 kinds) particle 17 thus, and enclosed in described tubule 15; Carry out the association reaction operation S33 of the association reaction of this particle 17 and described ASPE product; With the detection operation S34 detecting association reaction result.
As shown in Figure 13 (a), the test portion preparation process of step S31 comprises: the collection operation gathering the subjects such as such as oral mucosa, blood, nail from eight experimenters respectively; Extract the contained DNA such as this oral mucosa and carry out the amplification operation that increases respectively by PCR method; To the refining step that this DNA refines; ASPE method described later is used to be mixed with the ASPE product preparation process of ASPE product the DNA after refining.
With regard to described collection operation, such as, as shown in figure 13, by being suspended with the liquid of the described oral mucosa that gathers from eight experimenters etc., accommodating eight respectively and having in the box type container 92 of described well row 92a.Be cusp-shaped container 12 or point head of the various matter retaining bodies 11 of state of not enclosing by particle in described tubule 15, be installed on the nozzle 117 of described shower nozzle 84, suck the suspending liquid of the magnetic particle that surface is covered by the material such as porous material or silica respectively and be transplanted in each well row 92a, then spray simultaneously, drop into therefrom.
By making described drive plate 123 and plunger rod 112 move up and down, and described plunger 115a is moved up and down and repeatedly carries out suction ejection, thus, make described DNA be combined with magnetic particle and be captured.Now, make eight described magnetite 122b respectively close to each tubule 15 of eight described various matter retaining bodies 11, magnetic field is brought to its inside, thus, separated on the inwall that the described magnetic particle of catching described DNA is attracted to the tubule 15 of described cusp-shaped container 12.Catch the described magnetic particle of the described DNA after this separation by making described DNA deviate from, then DNA can be extracted and accommodate in the well row 96 of microplate.
Then, to each subject, by extracted DNA by PCR method, use the primer of specifying, increase in the mode obtaining four described DNA, collecting is afterwards in the left column of eight well row 99 of described microplate.In each well of the suspending liquid of the DNA after containing amplification, in order to remove the impurity containing the residue such as primer and oral mucosa, new cusp-shaped container 12 is installed on described shower nozzle 84, and plunger 115a is moved up and down and carries out the suction ejection of the suspending liquid of new magnetic particle, thus described DNA is caught by described magnetic particle.Now, use described comb teeth-shaped magnetite 122b to bring magnetic field in described cusp-shaped container 12, described magnetic particle is adsorbed on the inwall of described cusp-shaped container 12, thus is isolated and refines.
Then, ASPE(Allele-specific primer extension method is used) to the ASPE product 178 of each subject gene preparation for the determination of SNP everywhere described in carrying out.
As shown in Figure 13 (b), at 3 ' end, there is the base sequence 174 with base sequence 173 complementation of the tagDNA172 of a chain described later, there is at 5 ' end the base 175 of described SNP, with regard to the sequence between base sequence 174 and base 175, the synthetic DNA that the dozens of base preparing a chain of the patten's design of the base sequence of the contiguous complementary of the SNP becoming described each gene with four forms is as primer.Have the kind of many types of possibility, at this, each of four each genes has two kinds, and synthesis amounts to the primer of eight kinds, in each primer, comprises the base of a tagDNA172 and the corresponding SNP with eight kinds of mutual different regulation base sequences.The Dig-dUTP176 of this primer and replacement base " T " is used for base, according to each gene of each described subject, makes it extend amplification by PCR method.So, only a primer corresponding to the kind many types of with described subject DNA carries out elongation and increases, thus, described ASPE product 178 is configured to each of eight subjects.
Each subject of preparing ASPE product 178 is separately contained in the right-hand column of well row 99 of matrix form container 95 in advance.On the other hand, in eight well 100a of described box type container 100, the cleaning fluid that the detection operation containing step S34 described later in advance uses.In addition, in eight well 100b, contain in advance and identify anti-dig antibody 177 with the described AP of described Dig-dUTP176 specific binding, in eight well 100c, contain other cleaning fluid in advance, in described reagent resettlement section 77, contain matrix liquid 179(CDP-Star in advance).
In addition, in this embodiment, for each subject, contain eight kinds of whole mixed products of described ASPE product 178 in well row 99, but, such as, also can prepare to contain by four groups of every two kinds of mixed products of described ASPE product 178 different well row,, row relax of going forward side by side.
In step s 32, make the particle 17 that will accommodate and enclosed in described various matter retaining body 11.As shown in Figure 13 (b), the particle 17 that make is such as coated by avidin 171 and be combined with the particle of the tagDNA172 of the base sequence 173 of the regulation with biotinylation.At this, as described particle 17, such as, diameter is used to be roughly the size of about 1mm, the various resins such as such as nylon (Polysciences Inc.).In addition, pottery (Chiba Ceramic Corporation system, aluminium oxide: diameter 1.88mm) can such as be used.And, when using described light-proofness particle, such as, use the coloured glass of diameter 2.0mm.
In addition, the base sequence 174 of the base sequence 173 of each tagDNA172 and the complementation contained by described primer, has each of the many types of base of the possibility of SNP with described each gene, and the mode all with different base sequences 173,174 is synthesized.Like this, in the process of present embodiment, in SNP everywhere, for the many types of base of possibility separately with every two kinds, because of needs eight kinds of base sequences 173,174, therefore, eight kinds of particles 17 be made.
Eight kinds of described particles 17 are before inclosure, use the mark such as pigment, dyestuff material, color (purple, dark blue, green, yellow, red, blue or green, brown, orange) is such as utilized to carry out mutual discernible markization to each, in advance by the SNP one_to_one corresponding of various color and each gene.Such as, the particle of " purple " is corresponding with described Gene A Tase exon6 with the particle of Deep Blue, as tagDNA172, uses Tag1(base C respectively) and Tag3(base T); The particle of " green " and the particle of " Huang " corresponding with described Gene A Tase exon8, as tagDNA172, use Tag4(base A respectively) and Tag2(bases G); The particle of " red " and the particle of " green grass or young crops " corresponding with described gene C YP2C19 exon5, as tagDNA172, use Tag7(base A respectively) and Tag6(bases G); The particle of " brown " and the particle of " orange " corresponding with described gene C YP2D6 exon1, as tagDNA172, use Tag9(base C respectively) and Tag10(base T).
By the group combining eight kinds of particles 17 of the tagDNA172 of the base sequence 173 of eight kinds of described regulations with described biotinylation be made like this, need not special provision arrangement order and enclose in the described tubule 15 of described cusp-shaped container 12 randomly or in any order respectively, make eight various matter retaining bodies 11 thus, attach it on described shower nozzle 84, and be arranged in row.In order to enclose this particle 17, the group of eight kinds of described particles 17 to be accommodated from the extra heavy pipe 13 of described cusp-shaped container 12 can in the tubule 15 of loading and unloading after, undertaken by the bottom 18 of described extra heavy pipe 13 is entrenched togather with the fitting portion 15a of this tubule 15.In addition, when using light-proofness particle, the particle such as reacted and light-proofness particle are alternately arranged.
As described tubule 15, such as, use the described tubule 15 of polypropylene.The size of this tubule 15, such as, when using the particle of pottery of diameter 1.0mm, such as, adopts the circle of diameter 1.1mm.In addition, when using the particle of pottery of described diameter 1.88mm, the circle of diameter 2.0mm is adopted.And, when using the glass bead of described 2.0mm as light-proofness particle, adopt the circle of diameter 2.0mm.
In step S33, utilize moving part (not shown), each described oral area 16 that described shower nozzle 84 is arranged in eight described various matter retaining bodies 11 of row is moved to the position in each well of the well row 99 that can insert described matrix form container 95.Then, by described moving part (not shown), described oral area 16 is inserted in the lump in the well row 99 of described matrix form container 95.For described various matter retaining body 11, move up by making described plunger 115a, or by making it mobile along the vertical direction and repeatedly carrying out suction ejection, the mixed liquor of the ASPE product 178 making each subject accommodate contacts with each particle 17 in described various matter retaining body 11.Like this, described tagDNA172 base sequence 173 and and the described base sequence 173 of described ASPE product 178 have between complementary base sequence 174, cause hybridization reaction, deposit in case at each corresponding ASPE product 178 of described each particle 17, this ASPE product 178 combines.
Then, in step S34, utilize moving part (not shown), make described shower nozzle 84 move to the second well 100a of the described box type container 100 containing cleaning fluid along the described line direction as described mobile route, and described oral area 16 is inserted this second well 100a in the lump.Then, by making described plunger 115a move along the vertical direction, repeatedly carry out sucking, spraying and clean.
Then, described shower nozzle 84 is moved to eight the well 100b containing and identify the box type container 100 of anti-Dig antibody 177 with the described AP of described Dig-dUTP176 specific binding, described oral area 16 is made to be positioned at eight this well 100b and to insert together, described plunger 115a is utilized repeatedly to carry out suction ejection, thus, make described Dig-dUTP176 and described AP identify anti-Dig antibody 177 to be combined.Like this, described AP identifies many types of corresponding kind that anti-Dig antibody 177 only exists with each each subject and to combine and the ASPE product 178 obtained is combined with particle 17.In addition, shower nozzle 84 is moved to the well 100c of described box type container 100, make described oral area 16 be positioned at this well 100c and insert together, suction ejection is carried out repeatedly to accommodated cleaning fluid and cleans.
Then, utilize moving part (not shown), described shower nozzle 84 is made only to move the distance of a between-line spacing again along the described line direction as described mobile route, releasably being contained in by described various matter retaining body 11 is arranged in eight tip resettlement sections 102 of the position corresponding with the oral area 16 of described shower nozzle 84 along column direction, afterwards, carried by described conveyer 103, with when these eight tip resettlement sections 102 arrange in the row direction, described various matter retaining body 11 can be loaded and unloaded in described shower nozzle 84, the single nozzles be provided separately with eight nozzle block comes the mode of the position containing point head 78, described shower nozzle is moved integrally, and decline in this position, point head 78 is made only to be fitted together to thus, be installed on single nozzles, then, make shower nozzle 84 movement further, a described point head 78 is made to be positioned at described reagent resettlement section 77, then matrix liquid is drawn in point head 78 from this reagent resettlement section 77.
Utilize described moving part (not shown), this shower nozzle 84 is moved, successively matrix liquid 179 is dispensed into from the installation peristome 14 of accommodated eight described various matter retaining bodies 11 in the described tip resettlement section 102 arranged in the row direction, simultaneously, by described conveyer 103, carry eight described various matter retaining bodies 11 along described transport path.Like this, just at described measuring point 104, the chemiluminescence of being reacted by described matrix liquid 179 and described Dig and being produced about eight subjects can be detected successively.
In the step S34 of Figure 13, the measurement result of the subject gene of a people in eight subjects is taken into image and shown.Enclose the particle 17 of the described various matter retaining bodies 11 of this subject, if the first particle 17 to the eight particle 17 from top is by the order correspondence arrangement of described color (purple, dark blue, green, yellow, red, blue or green, brown, orange), so known, for the gene of this subject, for the first particle (purple), the 6th particle (green grass or young crops) and the 7th particle (brown), only detect very weak luminescence, therefore, the SNP of the Gene A Tase exon6 of this subject is base T; The SNP of Gene A Tase exon8 is base A/G; The SNP of gene C YP2C19 exon5 is base A; The SNP of gene C YP2D6 exon1 is base T.
In the example above, have employed Dig-dUDP and identify anti-Dig antibody with the AP of its specific binding, but, such as, HRP also can be adopted to identify anti-Dig antibody or POD and to identify anti-Dig antibody and replace AP to identify anti-Dig antibody.
Each embodiment discussed above is the embodiment carrying out to understand the present invention better specifically describing, but does not limit alternate manner.Therefore, can change in the scope of purport not changing invention.Such as, in said embodiment, only the situation of DNA, allergin and protein is illustrated, but also can is sugar chain, other DNA material, RNA etc.In addition, as particle shape carrier, only to spheroidal particle, and the situation that multiple particle shape carrier has same particle size is illustrated, but is not limited to this situation, and the shape of particle also can be cylindrical, the square bodily form, and particle not of uniform size causes also passable.In addition, unbodied particle shape carrier can be also applied to.In addition, about numerical value used in above explanation, number of times, shape, number, amount etc., these situations are also not limited to.In a word, can by the size of described oral area or installation peristome or shape as long as formed, and the suction of fluid and the particle of ejection can be carried out being held under the state in described carrier resettlement section, just can as described particle shape carrier use.
Moreover with regard to particle shape carrier, be only illustrated the situation of one dimensional arrangement, but be not limited to this situation, but, due in this case, the arrangement of chemical substance can be made during mensuration positively corresponding along one dimension path, and the reliability therefore measured is high.In addition, with regard to particle shape carrier, only the situation being contained in tubule is illustrated, but, core also can be set in extra heavy pipe or storing section, groove or ridge be set at the outer wall of core or the inwall of extra heavy pipe or storing section and form path, particle shape carrier is housed in this path.
In addition, above each inscape, each particle shape carrier, each tubule, cusp-shaped container, shower nozzle, sealing, nozzle etc., heating arrangement etc. or each device also can suitably carry out being out of shape or at random combining.In addition, part is also not limited to DNA, also comprises inhereditary material, immune substance, protein, the sugar chains such as oligomerization nucleotide, RNA, also comprises pheromones, allomone, mitochondria, virus, plasmid etc.
In addition, described reagent and material are the materials represented in example, use other reagent or material also passable.In addition, the carrier capturing DNA etc. can be taken out from described tubule etc. and preserve, as the object of other process.
Utilizability in industry
The present invention relates to various matter retaining body, various matter retaining body treating apparatus and disposal route thereof.The present invention relates to the boiomacromolecules such as gene, immune system, amino acid, protein, sugar, field required by biological low molecular process, such as, relate to industrial circle, the agriculture fields such as food, agricultural product, processing of aquatic products, medicine field, the medical fields such as health, health care, immunity, disease, heredity, the invention of all spectras such as field of science such as chemistry or biology.
Especially, when the order by regulation implements a series of process adopting multiple reagent or material continuously, the present invention is effective method.

Claims (9)

1. various matter retaining body treating apparatus, it has: have carry out gas suction, ejection the shower nozzle of one or more connected nozzle, the suction of gas, the suction emitting mechanism of ejection is carried out via described nozzle, with the set with multiple particle shape carrier or the many group particle shape carriers fixed and maybe can fix number of chemical material, and install and maybe can be arranged on described nozzle and it can be remained on one-dimensionally the carrier maintaining part of roughly stationary state from the set of particle shape carrier multiple described in external measurement or described many group particle shape carriers, each particle shape carrier of described multiple particle shape carrier or belong to each particle shape carrier of at least one of set of many group particle shape carriers, to import and before being held in described carrier maintaining part, according to the kind of described chemical substance, the set of each particle shape carrier or each particle shape carrier, by one or more various matter retaining bodies of mutual identifiably mark,
Described carrier maintaining part has cusp-shaped container and inclosure portion, described cusp-shaped container has the suction that can be arranged on and carry out gas, installation peristome on the described nozzle of ejection, with the suction by described gas, ejection and the inflow of fluid can be carried out, the oral area flowed out, described inclosure portion with can with the state of the fluid contact flowed into from described oral area, described particle shape carrier is enclosed in described carrier maintaining part, described cusp-shaped container has can store liquid and the storing section with described installation peristome, and to be communicated with described storing section and the tubule that described in the ratio with described oral area, storing section is thin, described particle shape carrier is maintained in described tubule,
Described various matter retaining body treating apparatus has: collecting maybe can accommodate the liquid storage portion group of various liquid; Make the mobile device of described shower nozzle and described liquid storage portion faciation movement over the ground; With based on by described various matter retaining body structure, be fixed on described particle shape carrier or be present in the kind of the various materials in fluid, material conditions that concentration, amount of liquid, the coordinate position that comprises the collecting position of described liquid are formed and contents processing, the amount sprayed the suction of described nozzle, speed, number of times, time or position control and the control part controlled temperature based on contents processing, and
When described carrier maintaining part is arranged on described nozzle, in the outside of described carrier maintaining part, also there is gradient of temperature body, described gradient of temperature body makes temperature rise according to the signal from outside, declines, can with carrier maintaining part near to or in contact with ground can arrange relative to the mode of various matter retaining body movement
Described mobile device makes described shower nozzle and described liquid storage portion relatively move, described gradient of temperature body can be made to move horizontally relative to described liquid storage portion together with shower nozzle, and can move along the vertical direction relative to described gradient of temperature body and described liquid storage portion group.
2. various matter retaining body treating apparatus as claimed in claim 1, it has: the receiving trap receiving the signal from the described particle shape carrier being held in described carrier maintaining part, and carries out the resolver of resolving based on the signal from described receiving trap.
3. various matter retaining body treating apparatus as claimed in claim 2, wherein, described resolver is according to the signal based on the first mark received by described receiving trap and resolve based on the signal of the second mark, described first mark is at described vector introduction and before being held in described carrier maintaining part, the mark that mutually can identify according to the set of the kind of described chemical substance, each described particle shape carrier or each particle shape carrier; Described second mark is at described vector introduction and after being held in described carrier maintaining part, by the mark of described particle shape signal of carrier.
4. various matter retaining body treating apparatus as claimed in claim 1, wherein, described shower nozzle is that multiple connected nozzle block and an independent nozzle form along column direction arrangement, described suction emitting mechanism carries out suction, the ejection of gas to the nozzle block of described shower nozzle and independent nozzle simultaneously, described mobile device has shower nozzle mobile device and ranks delivery pathways device, described shower nozzle mobile device makes described shower nozzle relatively move in the row direction for the platform with described liquid storage portion group, described ranks delivery pathways device have comprise described nozzle block mobile route on along the row transport path of described column direction, and along the transport path of the row transport path of described line direction on the mobile route of described single nozzles, and make can accommodate respectively and carry along described transport path from the cusp-shaped container that can load and unload in described nozzle block or from the conveying resettlement section of the liquid of described multiple connected nozzle block ejection.
5. various matter retaining body treating apparatus as claimed in claim 4, wherein, in the assigned position of the described transport path along described ranks delivery pathways device, be provided with the receiving trap received from the removably signal of described cusp-shaped container or described conveying resettlement section.
6. various matter retaining body disposal route, it has:
Installation procedure, in one or more carrier maintaining part, multiple particle shape carrier of number of chemical material or the set of many group particle shape carriers maybe can be fixed by fixing, can to measure in outside and roughly static state is held in tubule one-dimensionally, described carrier maintaining part has cusp-shaped container, described cusp-shaped container has and is arranged on shower nozzle, the suction carrying out gas can be arranged on, installation peristome on the nozzle of ejection, and by the suction of described gas, ejection and the inflow of fluid can be carried out, the oral area flowed out, described cusp-shaped container has can store liquid and the storing section with described installation peristome, and to be communicated with described storing section and the tubule that described in the ratio with described oral area, storing section is thin, and by each particle shape carrier of described multiple particle shape carrier or each particle shape carrier of at least one belonging to the set organizing particle shape carrier more, according to the kind of described chemical substance, the set of each described particle shape carrier or each described particle shape carrier, import and before being held in described carrier maintaining part by mutually identifiably one or more various matter retaining bodies of mark be installed on described nozzle by making shower nozzle move,
Reaction process, make to be arranged on described nozzle on described shower nozzle relative to liquid storage portion relative movement, and make the oral area of the various matter retaining body of described at least one move to the liquid storage portion of one or more regulation successively, thus make the liquid comes into contact in described particle shape carrier and liquid storage portion and react;
Resolve operation, resolve based on the received signal from each particle shape carrier be held in described carrier maintaining part, and,
Described reaction process has the gradient of temperature operation making the temperature in described carrier maintaining part rise, decline,
In described gradient of temperature operation, to be toward or away from from the carrier maintaining part of the outside described various matter retaining body with being arranged on described nozzle by making described gradient of temperature body and to carry out temperature control, described shower nozzle moves horizontally relative to described liquid storage portion group together with described gradient of temperature body relative to described liquid storage portion relative movement, and moves along the vertical direction relative to described gradient of temperature body and described liquid storage portion group.
7. various matter retaining body disposal route as claimed in claim 6, wherein, described reaction process is: the nozzle being provided with described various matter retaining body is moved to the liquid storage portion of specifying, based on the structure by described carrier maintaining part, be fixed on described particle shape carrier or be present in the kind of the chemical substance in liquid, concentration, amount of liquid, the material conditions that the position coordinates comprising the collecting position of described liquid is formed and contents processing, to comprising the amount sprayed via the suction of described nozzle, speed, number of times, the action of the suction ejection of time and position controls, thus, the chemical substance making to be fixed in described particle shape carrier be housed in the liquid comes into contact in described liquid storage portion and react.
8. various matter retaining body disposal route as claimed in claim 6, it has after described reaction process, receives the reception operation of the signal from the described particle shape carrier be maintained in described carrier maintaining part.
9. various matter retaining body disposal route as claimed in claim 8, wherein, described parsing operation according to receive in described reception operation, based on first mark signal and based on second mark signal resolve, described first mark is at described vector introduction and before being held in described carrier maintaining part, according to the mutual discernible mark of set of the kind of described chemical substance, each described particle shape carrier or each particle shape carrier; Described second mark is at described vector introduction and after being held in described carrier maintaining part, described particle shape carrier is carried out to the mark of markization.
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US20120252132A1 (en) 2012-10-04
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US8852525B2 (en) 2014-10-07
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US8828331B2 (en) 2014-09-09
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